The present invention concerns a method for evaluating a cancer patient for propensity to respond to therapy. The invention further concerns a method of monitoring efficiency of a treatment of cancer.

BACKGROUND TO THE INVENTION

Breast cancer is a major cause of morbidity and mortality in western countries. The application of taxane chemotherapy to the treatment of early-stage and advanced breast cancer has resulted in significant improvements in disease-free and overall survival. Taxanes (paclitaxel and docetaxel) are largely used in treatment of cancers such as breast cancer. However, pathologic complete response rates for single-agent taxanes are reduced.

In order to predict response of tumors to taxanes, gene signatures generated by gene expression profiling of tumor model cell lines have been developed.

Some signatures are as good or better than that achieved with clinical parameters alone (tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR), HER2, etc).

However, the use of gene signatures developed using model cell lines in the prognosis of tumoral cells to taxane resistance has been limited.

Model cell lines do not fully reflect the biology of breast tumors. Firstly, because those immortalized cells generally derive from metastasis and not from tumor cells. Additionally, because of the large diversity of tumor cells, numerous tumor breast cell types are not represented by any model cell line. Finally, the use of immortalized cells as biological model of cancer cells is biased in that during cell culture, immortalized cells may acquire mutations not present in original cancer cell.

Another disadvantage of model cell lines is that they do not take the natural environment of tumors into account. Tumoral epithelial cells interact with stromal cells or with the extracellular matrix. It has been demonstrated that stromal cells play a crucial role in tumor sensitivity or resistance to chemotherapeutic drugs.

Thus, there is a need for methods and markers for distinguishing drug-sensitive and drug-resistant tumors based on data from primary tumors are needed. BRIEF SUMMARY OF THE INVENTION

The invention concerns a method for predicting whether a cancer patient will respond to therapy, said method comprising determining the level of expression of at least one gene selected from the group consisting of procollagen-lysine, 2-oxoglutarate 5- dioxygenase 2 (PLOD2); imprinted maternally expressed transcript (H19); SIX homeobox 1 (SIX1 ); protocadherin alpha 1 (PCDHA1 ); S100 calcium binding protein A1 (S100A1 ); mitochondrial ribosomal protein S16 (MRPS16); thymidine kinase 2 (TK2); long intergenic non-protein coding RNA 589 (C8orf75); Cadherin 4 (CDH4); LOC100131756; zinc finger CCCH-type containing 12B (ZC3H12B); cation transport regulator homolog 2 (CHAC2); eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2); protocadherin beta 15 (PCDHB15); vestigial like 4 (VGLL4); Janus kinase 1 (JAK1 ); apolipoprotein L, 6 (APOL6); cyclin O (CCNO); protocadherin beta 14 (PCDHB14); integrin alpha 4 (ITGA4); protocadherin beta 18 (PCDHB18); peptidylprolyl isomerase F (PPIF); ras homolog family member U (RHOU); ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4); transmembrane protein 63A (TMEM63A); ribosomal protein S6 kinase-like 1 (RPS6KL1 ); centrosome and spindle pole associated protein 1 (CSPP1 ); fucosyltransferase 6 (FUT6); SID1 transmembrane family, member 2 (SIDT2); hepatitis A virus cellular receptor 2 (HAVCR2); chromosome 5 open reading frame 4 (C5orf4); carboxylesterase 3 (CES3); chromosome 14 open reading frame 39 (C14orf39); T cell receptor delta locus (TRD@) and transporter 2, ATP-binding cassette, sub-family B (TAP2) in a biological sample from the patient.

The invention also concerns a method of monitoring efficiency of cancer therapy comprising:

a) determining the expression level of at least one gene selected from the group consisting of SIX1 ; PLOD2; H19; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75;

CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ;

APOL6; CCNO; PCDHB14; ITGA4; PCDHB18;PPIF; RHOU; ST8SIA4; TMEM63A;

RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and

TAP2 in a biological sample from a patient undergoing said therapy,

b) repeating step a) on another biological sample from the same patient taken at a later point in time,

wherein an alteration of the expression level of said gene(s) is indicative of the efficacy of said therapy. Also provided is a method of prognosing or classifying the outcome of cancer in a patient undergoing a therapy comprising a treatment with a taxane, said method comprises the step of determining the level of expression of at least one gene selected from the group consisting of SIX1 ; PLOD2; H19; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 in a biological sample from the patient.

The invention also concerns a method for determining a therapeutic regimen suitable for treating a subject suffering from a cancer, wherein said method comprises the steps of:

a) predicting whether said patient will respond to a therapy using the method for predicting whether a cancer patient will respond to therapy according to the invention, and b) deducing a suitable therapeutic regimen for the subject.

Also provided is a panel of cancer therapy markers, said panel comprising or consisting of at least one marker selected from the group consisting of SIX1 ; PLOD2; H19; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2.

The invention further provides a kit for predicting responsiveness of a cancer patient to a therapy comprising a treatment with a taxane, said kit comprising means for detecting the panel of markers according to the invention.

DETAILED DESCRIPTION OF THE INVENTION The inventors have developed a reproducible method of analyzing tumoral fragments with the intent of identifying markers of response to taxane therapy. Said method provides representative results because, during the assay, the natural tumoral cell environment is preserved and cells can be cultured up to 48 hours, a duration long enough to study the biological response of tumoral cells to drug therapy. Using this method, the inventors have found that specific genes were deregulated in tumoral cells and that this deregulation is indicative of the resistance or sensitivity of tumoral cells to taxane therapy. The inventors have reported that 35 genes were deregulated in breast cancer cells sensitive to taxanes compared with breast cancer resistant cells. Thus, the invention relates to a method for predicting whether a cancer patient will respond to therapy, said method comprising determining the level of expression of at least one gene selected from the group consisting of SIX1 ; PLOD2; H19; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 in a biological sample from the patient.Typically, said method comprises determining the level of expression of at least PLOD2 and TK2; or at least PLOD2 and SIX1 ; or at least PLOD2 and JAK1 ; or at least TK2 and SIX1 ; or at least TK2 and JAK1 ; or at least SIX1 and JAK1 ; or at least SIX1 ; PLOD2 and TK2; or at least SIX1 , PLOD2 and JAK1 ; or at least SIX1 , TK2 and JAK1 ; or at least TK2, PLOD2 and JAK1 ; or at least SIX1 , PLOD2; TK2 and JAK1 ; or PLOD2, JAK1 and H19; or at least PLOD2, SIX1 and JAK1 ; or at least PLOD2, SIX1 and PCDHA1 ; or at least PLOD2, SIX1 and S100A1 ; or at least PLOD2, JAK1 and MRPS16; or at least PLOD2, SIX1 and TK2; or at least PLOD2, SIX1 and C8orf75; or at least PLOD2, SIX1 and CDH4; or at least PLOD2, SIX1 and LOC100131756; or at least PLOD2, SIX1 and ZC3H12B; or at least PLOD2, SIX1 and CHAC2; or at least PLOD2, JAK1 and EIF2AK2; or at least PLOD2, SIX1 and PCDHB15; or at least PLOD2, SIX1 and VGLL4; or at least PLOD2, RHOU and SIX1 ; or at least PLOD2, SIX1 and APOL6; or at least PLOD2, JAKI and ST8SIA4; or at least PLOD2, SIX1 and CCNO; or at least PLOD2, JAK1 and PCDHB14; or at least PLOD2, SIX1 and ITGA4; or at least PLOD2, JAK1 and PCDHB18; or at least PLOD2, SIX1 and PPIF; or at least PLOD2, SIX1 and TMEM63A; or at least PLOD2, SIX1 and RPS6KL1 ; or at least PLOD2, RHOU and CSPP1 ; or at least PLOD2, SIX1 and FUT6; or at least PLOD2, SIX1 and SIDT2; or at least PLOD2, SIX1 and HAVCR2; or at least PLOD2, SIX1 and C5orf4; or at least PLOD2, SIX1 and CES3; or at least PLOD2, SIX1 and C14orf39; or at least PLOD2, SIX1 and TRD@; or at least PLOD2, SIX1 and TAP2 in a biological sample from the patient.

The agent used for therapy is preferably an antiproliferative and/or anti-angiogenic agent, for example a taxane.

As used herein, the term " taxane" means paclitaxel, docetaxel, or other taxanes that may be either isolated from natural sources such as the Yew tree, or from cell culture, or chemically synthesized, such as 10-deacetylpaclitaxel, 7-epipaclitaxel, cephalomannine, 7-epi-cephalomannine, and N-debenzoyl-N-phenylacetylpaclitaxel. The most preferred taxane is paclitaxel. Paclitaxel refers to paclitaxel (CAS N ° 33069-62-4), analogues and derivatives thereof, including, for example, a natural or synthetic functional analogue of paclitaxel which has paclitaxel biological activity, as well as a fragment of paclitaxel having paclitaxel biological activity. A compound which is a paclitaxel analogue refers to a compound which interferes with cellular mitosis by affecting microtubule formation and/or action, thereby producing antimitotic and anti-cellular proliferation effects. Methods of preparing paclitaxel and its analogues and derivatives are well-known in the art. Moreover, Paclitaxel, its analogues and derivatives are also available commercially. Synthetic paclitaxel, for example, can be obtained from Bristol-Myers Squibb Company, Oncology Division (Princeton, NJ), under the registered trademark Taxol®.

In one embodiment, the method of the invention comprises the step of determining the level of expression of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35genes selected from the group consisting of PLOD2; H19; SIX1; PCDHA1; S100A1; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; IF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1; CSPP1; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 or one variant thereof. Typically, the method of the invention comprises the step of determining the level of expression of at least PLOD2, JAK1, SIX1, TK2 and CDH4; or PLOD2, JAK1, SIX1, TK2 and LOC100131756; or PLOD2, JAK1, SIX1, TK2 and ZC3H12B; or PLOD2, JAK1, SIX1, TK2 and CHAC2; or PLOD2, JAK1, SIX1, TK2 and EIF2AK2; or PLOD2, JAK1, SIX1, TK2 and PCDHB15; or PLOD2, JAK1, SIX1, TK2 and VGLL4; or PLOD2, JAK1, SIX1, TK2 and H19; or PLOD2, JAK1, SIX1, TK2 and APOL6; or PLOD2, JAK1, SIX1, TK2 and ST8SIA4; or PLOD2, JAK1, SIX1, TK2 and CCNO; or PLOD2, JAK1, SIX1, TK2 and PCDHB14; or PLOD2, JAK1, SIX1, TK2 and ITGA4; or PLOD2, JAK1, SIX1, TK2 and PCDHB18; or PLOD2, JAK1, SIX1, TK2 and PPIF; or PLOD2, JAK1, SIX1, TK2 and RHOU; or PLOD2, JAK1, SIX1, TK2 and TMEM63A; or PLOD2, JAK1, SIX1, TK2 and RPS6KL1 ; or PLOD2, JAK1, SIX1, TK2 and CSPP1; or PLOD2, JAK1, SIX1, TK2 and FUT6; or PLOD2, JAK1, SIX1, TK2 and SIDT2; or PLOD2, JAK1, SIX1, TK2 and HAVCR2; or PLOD2, JAK1, SIX1, TK2 and C5orf4; or PLOD2, JAK1, SIX1, TK2 and CES3; or PLOD2, JAK1, SIX1, TK2 and C14orf39; or PLOD2, JAK1, SIX1, TK2 and TRD@; or PLOD2, JAK1, SIX1, TK2 and TAP2; or PLOD2, S100A1, SIX1, PCDHA1 and MRPS16; or PLOD2, S100A1, SIX1, PCDHA1 and TK2; or PLOD2, S100A1, SIX1, PCDHA1 and C8orf75; or PLOD2, S100A1, SIX1, PCDHA1 and CDH4; or PLOD2, S100A1, SIX1, PCDHA1 and LOC100131756; or PLOD2, S100A1, SIX1, PCDHA1 and ZC3H12B; or PLOD2, S100A1, SIX1, PCDHA1 and CHAC2; or PLOD2, S100A1, SIX1, PCDHA1 and EIF2AK2; or PLOD2, S100A1, SIX1, PCDHA1 and PCDHB15; or PLOD2, S100A1, SIX1, PCDHA1 and VGLL4; or PLOD2, S100A1, SIX1, PCDHA1 and JAK1; or PLOD2, S100A1, SIX1, PCDHA1 and APOL6; or PLOD2, S100A1, SIX1, PCDHA1 and ST8SIA4; or PLOD2, S100A1, SIX1, PCDHA1 and CCNO; or PLOD2, S100A1, SIX1, PCDHA1 and PCDHB14; or PLOD2, S100A1, SIX1, PCDHA1 and ITGA4; or PLOD2, S100A1, SIX1, PCDHA1 and PCDHB18; or PLOD2, S100A1, SIX1, PCDHA1 and PPIF; or PLOD2, S100A1, SIX1, PCDHA1 and RHOU; or PLOD2, S100A1, SIX1, PCDHA1 and TMEM63A; or PLOD2, S100A1, SIX1, PCDHA1 and RPS6KL1; or PLOD2, S100A1, SIX1, PCDHA1 and CSPP1; or PLOD2, S100A1, SIX1, PCDHA1 and FUT6; or PLOD2, S100A1 , SIX1 , PCDHA1 and SIDT2; or PLOD2, S100A1 , SIX1, PCDHA1 and HAVCR2; or PLOD2, S100A1, SIX1, PCDHA1 and C5orf4; or PLOD2, S100A1, SIX1, PCDHA1 and CES3; or PLOD2, S100A1, SIX1, PCDHA1 and C14orf39; or PLOD2, S100A1, SIX1, PCDHA1 and TRD@; or PLOD2, S100A1, SIX1, PCDHA1 and TAP2; or PLOD2, MRPS16, SIX1, PCDHA1 , and S100A1; or MRPS16, SIX1, PCDHA1 and TK2; or PLOD2, MRPS16, SIX1, PCDHA1 and C8orf75; or PLOD2, MRPS16, SIX1, PCDHA1 and CDH4; or PLOD2, MRPS16, SIX1, PCDHA1 and LOC100131756; or PLOD2, MRPS16, SIX1, PCDHA1 and ZC3H12B; or PLOD2, MRPS16, SIX1, PCDHA1 and CHAC2; or PLOD2, MRPS16, SIX1, PCDHA1 and EIF2AK2; or PLOD2, MRPS16, SIX1, PCDHA1 and PCDHB15; or PLOD2, MRPS16, SIX1, PCDHA1 and VGLL4; or PLOD2, MRPS16, SIX1, PCDHA1 and JAK1; or PLOD2, MRPS16, SIX1, PCDHA1 and APOL6; or PLOD2, MRPS16, SIX1, PCDHA1 and ST8SIA4; or PLOD2, MRPS16, SIX1, PCDHA1 and CCNO; or PLOD2, MRPS16, SIX1, PCDHA1 and PCDHB14; or PLOD2, MRPS16, SIX1, PCDHA1 and ITGA4; or PLOD2, MRPS16, SIX1, PCDHA1 and PCDHB18; or PLOD2, MRPS16, SIX1, PCDHA1 and PPIF; or PLOD2, MRPS16, SIX1, PCDHA1 and TK2; or PLOD2, MRPS16, SIX1, PCDHA1 and TMEM63A; or PLOD2, MRPS16, SIX1, PCDHA1 and RPS6KL1 ; or PLOD2, MRPS16, SIX1, PCDHA1 and CSPP1; or PLOD2, MRPS16, SIX1, PCDHA1 and FUT6; or PLOD2, MRPS16, SIX1, PCDHA1 and SIDT2; or PLOD2, MRPS16, SIX1, PCDHA1 and HAVCR2; or PLOD2, MRPS16, SIX1, PCDHA1 and C5orf4; or PLOD2, MRPS16, SIX1, PCDHA1 and CES3; or PLOD2, MRPS16, SIX1, PCDHA1 and C14orf39; or PLOD2, MRPS16, SIX1, PCDHA1 and TRD@; or PLOD2, MRPS16, SIX1, PCDHA1 and TAP2; or PLOD2, TK2, SIX1, PCDHA1 , and S100A1; or PLOD2, TK2, SIX1, PCDHA1 and MRPS16; orPLOD2, TK2, SIX1, PCDHA1 and TK2; or PLOD2, TK2, SIX1, PCDHA1 and C8orf75; or PLOD2, TK2, SIX1, PCDHA1 and CDH4; or PLOD2, TK2, SIX1, PCDHA1 and LOC100131756; or PLOD2, TK2, SIX1, PCDHA1 and ZC3H12B; or PLOD2, TK2, SIX1, PCDHA1 and CHAC2; or PLOD2, TK2, SIX1, PCDHA1 and EIF2AK2; or PLOD2, TK2, SIX1, PCDHA1 and PCDHB15; or PLOD2, TK2, SIX1, PCDHA1 and VGLL4; or PLOD2, TK2, SIX1, PCDHA1 and JAK1 ; or PLOD2, TK2, SIX1, PCDHA1 and APOL6; or PLOD2, TK2, SIX1, PCDHA1 and ST8SIA4; or PLOD2, TK2, SIX1, PCDHA1 and CCNO; or PLOD2, TK2, SIX1, PCDHA1 and PCDHB14; or PLOD2, TK2, SIX1, PCDHA1 and ITGA4; or PLOD2, TK2, SIX1, PCDHA1 and PCDHB18; or PLOD2, TK2, SIX1, PCDHA1 and PPIF; or PLOD2, TK2, SIX1, PCDHA1 and TMEM63A; or PLOD2, TK2, SIX1, PCDHA1 and RPS6KL1 ; or PLOD2, TK2, SIX1, PCDHA1 and CSPP1; or PLOD2, TK2, SIX1, PCDHA1 and FUT6; or PLOD2, TK2, SIX1, PCDHA1 and SIDT2; or PLOD2, TK2, SIX1, PCDHA1 and HAVCR2; or PLOD2, TK2, SIX1, PCDHA1 and C5orf4; or PLOD2, TK2, SIX1, PCDHA1 and CES3; or PLOD2, TK2, SIX1, PCDHA1 and C14orf39; or PLOD2, TK2, SIX1, PCDHA1 and TRD@; or PLOD2, TK2, SIX1, PCDHA1 and TAP2; or PLOD2, MRPS16, SIX1, PCDHB15, and S100A1 ; or MRPS16, SIX1, PCDHB15 and TK2; or PLOD2, MRPS16, SIX1, PCDHB15 and C8orf75; or PLOD2, MRPS16, SIX1, PCDHB15 and CDH4; or PLOD2, MRPS16, SIX1, PCDHB15 and LOC100131756; or PLOD2, MRPS16, SIX1, PCDHB15 and ZC3H12B; or PLOD2, MRPS16, SIX1, PCDHB15 and CHAC2; or PLOD2, MRPS16, SIX1, PCDHB15 and EIF2AK2; or PLOD2, MRPS16, SIX1, PCDHB15 and PCDHB15; or PLOD2, MRPS16, SIX1, PCDHB15 and VGLL4; or PLOD2, MRPS16, SIX1, PCDHB15and JAK1; or PLOD2, MRPS16, SIX1, PCDHB15and APOL6; or PLOD2, MRPS16, SIX1, PCDHB15 and ST8SIA4; or PLOD2, MRPS16, SIX1, PCDHB15 and CCNO; or PLOD2, MRPS16, SIX1, PCDHB15 and PCDHB14; or PLOD2, MRPS16, SIX1, PCDHB15 and ITGA4; or PLOD2, MRPS16, SIX1, PCDHB15 and PCDHB18; or PLOD2, MRPS16, SIX1, PCDHB15 and PPIF; or PLOD2, MRPS16, SIX1, PCDHB15 and TK2; or PLOD2, MRPS16, SIX1, PCDHB15 and TMEM63A; or PLOD2, MRPS16, SIX1, PCDHB15 and RPS6KL1 ; or PLOD2, MRPS16, SIX1, PCDHB15 and CSPP1; or PLOD2, MRPS16, SIX1, PCDHB15 and FUT6; or PLOD2, MRPS16, SIX1, PCDHB15 and SIDT2; or PLOD2, MRPS16, SIX1, PCDHB15 and HAVCR2; or PLOD2, MRPS16, SIX1 , PCDHB15 and C5orf4; or PLOD2, MRPS16, SIX1 , PCDHB15 and CES3; or PLOD2, MRPS16, SIX1, PCDHB15 and C14orf39; or PLOD2, MRPS16, SIX1, PCDHB15 and TRD@; or PLOD2, MRPS16, SIX1 , PCDHB15 and TAP2.

Typically, the method of the invention comprises the step of determining the level of expression of at least TRD@, H19, SIX1, TK2 and CDH4; or TRD@, H19, SIX1, TK2 and LOC100131756; or TRD@, H19, SIX1, TK2 and ZC3H12B; or TRD@, H19, SIX1, TK2 and CHAC2; or TRD@, H19, SIX1, TK2 and EIF2AK2; or TRD@, H19, SIX1, TK2 and PCDHB15; or TRD@, H19, SIX1, TK2 and VGLL4; or TRD@, H19, SIX1, TK2 and JAK1; or TRD@, H19, SIX1, TK2 and APOL6; or TRD@, H19, SIX1 , TK2 and ST8SIA4; or TRD@, H19, SIX1, TK2 and CCNO; or TRD@, H19, SIX1, TK2 and PCDHB14; or TRD@, H19, SIX1,TK2and ITGA4; or TRD@, H19, SIX1 , TK2 and PCDHB18; or TRD@, H19, SIX1 , TK2 and PPIF; or TRD@, H19, SIX1 and TK2 ; or TRD@, H19, SIX1 , TK2 and TMEM63A; or TRD@, H19, SIX1, TK2 and RPS6KL1; or TRD@, H19, SIX1, TK2 and CSPP1; or TRD@, H19, SIX1, TK2 and FUT6; or TRD@, H19, SIX1, TK2 and SIDT2; or TRD@, H19, SIX1 , TK2 and HAVCR2; or TRD@, H19, SIX1 , TK2 and C5orf4; or TRD@, H19, SIX1, TK2 and CES3; or TRD@, H19, SIX1, TK2 and C14orf39; or TRD@, H19, SIX1 , TK2 and TRD@; or TRD@, H19, SIX1 , TK2 and TAP2; or TRD@, S100A1 , SIX1 , PCDHA1 and MRPS16; or TRD@, S100A1 , SIX1 , PCDHA1 and TK2; or TRD@, S100A1 , SIX1, PCDHA1 and C8orf75; or TRD@, S100A1, SIX1, PCDHA1 and CDH4; or TRD@, S100A1, SIX1, PCDHA1 and LOC100131756; or TRD@, S100A1, SIX1, PCDHA1 and ZC3H12B; or TRD@, S100A1, SIX1, PCDHA1 and CHAC2; or TRD@, S100A1, SIX1, PCDHA1 and EIF2AK2; or TRD@, S100A1, SIX1, PCDHA1 and PCDHB15; or TRD@, S100A1, SIX1, PCDHA1 and VGLL4; or TRD@, S100A1, SIX1, PCDHA1 and JAK1 ; or TRD@, S100A1, SIX1, PCDHA1 and APOL6; or TRD@, S100A1, SIX1, PCDHA1 and ST8SIA4; or TRD@, S100A1, SIX1, PCDHA1 and CCNO; or TRD@, S100A1, SIX1, PCDHA1 and PCDHB14; or TRD@, S100A1, SIX1, PCDHA1 and ITGA4; or TRD@, S100A1, SIX1, PCDHA1 and PCDHB18; or TRD@, S100A1, SIX1, PCDHA1 and PPIF; or TRD@, S100A1, SIX1, PCDHA1 and C14orf39; or TRD@, S100A1, SIX1, PCDHA1 and TMEM63A; or TRD@, S100A1 , SIX1 , PCDHA1 and RPS6KL1 ; or TRD@, S100A1 , SIX1 , PCDHA1 and CSPP1 ; or TRD@, S100A1 , SIX1 , PCDHA1 and FUT6; or TRD@, S100A1 , SIX1 , PCDHA1 and SIDT2; or TRD@, S100A1 , SIX1 , PCDHA1 and HAVCR2; or TRD@, S100A1, SIX1, PCDHA1 and C5orf4; or TRD@, S100A1, SIX1, PCDHA1 and CES3; or TRD@, S100A1, SIX1, PCDHA1 and C14orf39; or TRD@, S100A1, SIX1, PCDHA1 and TAP2; or TRD@, MRPS16, SIX1, PCDHA1 , and S100A1; or MRPS16, SIX1, PCDHA1 and TK2; or TRD@, MRPS16, SIX1, PCDHA1 and C8orf75; or TRD@, MRPS16, SIX1, PCDHA1 and CDH4; or TRD@, MRPS16, SIX1, PCDHA1 and LOC100131756; or TRD@, MRPS16, SIX1, PCDHA1 and ZC3H12B; or TRD@, MRPS16, SIX1, PCDHA1 and CHAC2; or TRD@, MRPS16, SIX1, PCDHA1 and EIF2AK2; or TRD@, MRPS16, SIX1, PCDHA1 and PCDHB15; or TRD@, MRPS16, SIX1, PCDHA1 and VGLL4; or TRD@, MRPS16, SIX1, PCDHA1 and JAK1; or TRD@, MRPS16, SIX1, PCDHA1 and APOL6; or TRD@, MRPS16, SIX1, PCDHA1 and ST8SIA4; or TRD@, MRPS16, SIX1, PCDHA1 and CCNO; or TRD@, MRPS16, SIX1, PCDHA1 and PCDHB14; or TRD@, MRPS16, SIX1, PCDHA1 and ITGA4; or TRD@, MRPS16, SIX1, PCDHA1 and PCDHB18; or TRD@, MRPS16, SIX1, PCDHA1 and PPIF; or TRD@, MRPS16, SIX1 and PCDHA1 ; or TRD@, MRPS16, SIX1, PCDHA1 and TMEM63A; or TRD@, MRPS16, SIX1, PCDHA1 and RPS6KL1; or TRD@, MRPS16, SIX1, PCDHA1 and CSPP1; or TRD@, MRPS16, SIX1, PCDHA1 and FUT6; or TRD@, MRPS16, SIX1, PCDHA1 and SIDT2; or TRD@, MRPS16, SIX1, PCDHA1 and HAVCR2; or TRD@, MRPS16, SIX1, PCDHA1 and C5orf4; or TRD@, MRPS16, SIX1, PCDHA1 and CES3; or TRD@, MRPS16, SIX1 , PCDHA1 and C14orf39; or TRD@, MRPS16, SIX1 , PCDHA1 and TRD@; or TRD@, MRPS16, SIX1 , PCDHA1 and TAP2; or TRD@, , SIX1 , PCDHA1 , and S100A1 ; or TRD@, , SIX1, PCDHA1 and MRPS16; orTRD@, C14orf39, SIX1, PCDHA1 and TK2; or TRD@, C14orf39, SIX1, PCDHA1 and C8orf75; or TRD@, C14orf39, SIX1, PCDHA1 and CDH4; or TRD@, C14orf39, SIX1, PCDHA1 and LOC100131756; or TRD@, C14orf39, SIX1, PCDHA1 and ZC3H12B; or TRD@, , SIX1, PCDHA1 and CHAC2; or TRD@, C14orf39, SIX1, PCDHA1 and EIF2AK2; or TRD@, , SIX1, PCDHA1 and PCDHB15; or TRD@, , SIX1, PCDHA1 and VGLL4; or TRD@, , SIX1, PCDHA1 and JAK1 ; or TRD@, , SIX1 , PCDHA1 and APOL6; or TRD@, C14orf39, SIX1 , PCDHA1 and ST8SIA4; or TRD@, , SIX1, PCDHA1 and CCNO; or TRD@, C14orf39, SIX1, PCDHA1 and PCDHB14; or TRD@, , SIX1, PCDHA1 and ITGA4; or TRD@, , SIX1, PCDHA1 and PCDHB18; or TRD@, C14orf39, SIX1, PCDHA1 and PPIF; or TRD@, C14orf39, SIX1, PCDHA1 and TMEM63A; or TRD@, , SIX1, PCDHA1 and RPS6KL1; or TRD@, C14orf39, SIX1, PCDHA1 and CSPP1 ; or TRD@, C14orf39, SIX1, PCDHA1 and FUT6; or TRD@, C14orf39, SIX1, PCDHA1 and SIDT2; or TRD@, , SIX1, PCDHA1 and HAVCR2; or TRD@, C14orf39, SIX1, PCDHA1 and C5orf4; or TRD@, , SIX1, PCDHA1 and CES3; or TRD@, or TRD@, SIX1, PCDHA1 and TAP2; or TRD@, MRPS16, SIX1, PCDHB15, and S100A1; or MRPS16, SIX1, PCDHB15 and TK2; or TRD@, MRPS16, SIX1, PCDHB15 and C8orf75; or TRD@, MRPS16, SIX1, PCDHB15 and CDH4; or TRD@, MRPS16, SIX1, PCDHB15 and LOC100131756; or TRD@, MRPS16, SIX1, PCDHB15 and ZC3H12B; or TRD@, MRPS16, SIX1, PCDHB15 and CHAC2; or TRD@, MRPS16, SIX1, PCDHB15 and EIF2AK2; or TRD@, MRPS16, SIX1, PCDHB15 and PCDHB15; or TRD@, MRPS16, SIX1, PCDHB15 and VGLL4; or TRD@, MRPS16, SIX1, PCDHB15 and JAK1 ; or TRD@, MRPS16, SIX1, PCDHB15 and APOL6; or TRD@, MRPS16, SIX1, PCDHB15 and ST8SIA4; or TRD@, MRPS16, SIX1, PCDHB15 and CCNO; or TRD@, MRPS16, SIX1, PCDHB15 and PCDHB14; or TRD@, MRPS16, SIX1, PCDHB15 and ITGA4; or TRD@, MRPS16, SIX1, PCDHB15 and PCDHB18; or TRD@, MRPS16, SIX1, PCDHB15 and PPIF; or TRD@, MRPS16, SIX1 and PCDHB15 and C14orf39; or TRD@, MRPS16, SIX1, PCDHB15 and TMEM63A; or TRD@, MRPS16, SIX1, PCDHB15 and RPS6KL1 ; or TRD@, MRPS16, SIX1, PCDHB15 and CSPP1 ; or TRD@, MRPS16, SIX1, PCDHB15 and FUT6; or TRD@, MRPS16, SIX1, PCDHB15 and SIDT2; or TRD@, MRPS16, SIX1, PCDHB15 and HAVCR2; or TRD@, MRPS16, SIX1, PCDHB15 and C5orf4; or TRD@, MRPS16, SIX1, PCDHB15 and CES3; or PLOD2, MRPS16, SIX1, PCDHB15and C14orf39; or TRD@, MRPS16, SIX1, PCDHB15 and TAP2. In one embodiment, the level of expression of said gene(s) is determined by detecting transcription product(s) and/or translation product(s) of said gene(s). Level of expression of gene can be performed by methods which are well known to the person skilled in the art, including in particular quantitative methods involving reverse transcriptase PCR (RT-PCR), such as real-time quantitative RT-PCR (qRT-PCR), and methods involving the use of DNA arrays (macroarrays or microarrays) and In Situ hybridizations.

Level of expression of gene(s) may further be assessed by using immunologic methods such as detection using polyclonal or monoclonal antibodies. Suitable immunologic methods include enzyme linked immunoassays (ELISA), sandwich, direct, indirect, or competitive ELISA assays, enzyme linked immunospotassays (ELIspot), radio immunoassays (RIA), flow-cytometry assays (FACS), immunohistochemistry, Western Blot, fluorescence resonance energy transfer (FRET) assays, protein chip assays using for example antibodies, antibody fragments, receptor ligands or other agents binding the proteins coded by the genes of table 1 .

In certain embodiments, a "gene" refers to a nucleic acid that is transcribed. In certain aspects, the gene includes regulatory sequences involved in transcription, or message production or composition. In particular embodiments, the gene comprises transcribed sequences that encode for a protein, polypeptide or peptide. In other particular aspects, the gene comprises a nucleic acid, and/or encodes a polypeptide or peptide- coding sequences of a gene that is defective or mutated in a hematopoietic and lympho- hematopoietic disorder. In keeping with the terminology described herein, an "isolated gene" may comprise transcribed nucleic acid(s), regulatory sequences, coding sequences, or the like, isolated substantially away from other such sequences, such as other naturally occurring genes, regulatory sequences, polypeptide or peptide encoding sequences, etc. In this respect, the term "gene" is used for simplicity to refer to a nucleic acid comprising a nucleotide sequence that is transcribed, and the complement thereof. In particular aspects, the transcribed nucleotide sequence comprises at least one functional protein, polypeptide and/or peptide encoding unit. As will be understood by those in the art, this functional term "gene" includes both genomic sequences, RNA or cDNA sequences, or smaller engineered nucleic acid segments, including nucleic acid segments of a non-transcribed part of a gene, including but not limited to the non-transcribed promoter or enhancer regions of a gene. Smaller engineered gene nucleic acid segments may express, or may be adapted to express using nucleic acid manipulation technology, proteins, polypeptides, domains, peptides, fusion proteins, mutants and/or such like. For example, when the level of expression of said gene(s) is determined by detecting transcription product(s), said transcription product is a nucleic acid comprising a sequence or a sequence complementary to SEQ ID NO : 1 ; SEQ ID NO : 3

SEQ ID NO : 4; SEQ ID NO : 6; SEQ ID NO : 8; SEQ ID NO : 10; SEQ ID NO : 12

SEQ ID NO : 14 SEQ ID NO : 16 SEQ ID NO 18 SEQ ID NO : 19 SEQ ID NO : 21

SEQ ID NO : 23 SEQ ID NO : 25 SEQ ID NO 27 SEQ ID NO : 29 SEQ ID NO : 31

SEQ ID NO : 33 SEQ ID NO : 35 SEQ ID NO 37 SEQ ID NO : 39 SEQ ID NO : 41

SEQ ID NO : 43 SEQ ID NO : 45 SEQ ID NO 47 SEQ ID NO : 49 SEQ ID NO : 51

SEQ ID NO : 53 SEQ ID NO : 55 SEQ ID NO 57 SEQ ID NO : 59 SEQ ID NO : 61

SEQ ID NO : 63 SEQ ID NO : 65; SEQ ID NO : 66; or a variant or fragment thereof, preferably of said transcription product is a nucleic acid comprising a sequence or a sequence complementary to at least one, 2, 3 or 4 sequence(s) SEQ ID NO : 1 ; SEQ ID NO : 4; SEQ ID NO : 12; SEQ ID NO : 29; or a variant or fragment thereof.

The term "nucleic acid" will generally refer to at least one molecule or strand of DNA, RNA or a derivative or mimic thereof, comprising at least one nucleobase, such as, for example, a naturally occurring purine or pyrimidine base found in DNA (e.g., adenine "A," guanine "G," thymine "T," and cytosine "C") or RNA (e.g. A, G, uracil "U," and C). The term "nucleic acid" encompasses the terms "oligonucleotide" and "polynucleotide." The term "oligonucleotide" refers to at least one molecule of between about 3 and about 100 nucleobases in length. The term "polynucleotide" refers to at least one molecule of greater than about 100 nucleobases in length. These definitions generally refer to at least one single-stranded molecule, but in specific embodiments will also encompass at least one additional strand that is partially, substantially or fully complementary to the at least one single-stranded molecule. Thus, a nucleic acid may encompass at least one double- stranded molecule or at least one triple-stranded molecule that comprises one or more complementary strand(s) or "complement(s)" of a particular sequence comprising a strand of the molecule.

A nucleic acid may be made by any technique known to one of ordinary skill in the art. Non-limiting examples of synthetic nucleic acid, particularly a synthetic oligonucleotide, include a nucleic acid made by in vitro chemical synthesis using phosphotriester, phosphite or phosphoramidite chemistry and solid phase techniques such described by Froehler et at., 1986 via deoxynucleoside H-phosphonate intermediates. A non-limiting example of enzymatically produced nucleic acid include one produced by enzymes in amplification reactions such as PCR™ or the synthesis of oligonucleotides. A non-limiting example of a biologically produced nucleic acid includes recombinant nucleic acid production in living cells (see for example, Sambrook et al. 2000). A nucleic acid may be purified on polyacrylamide gels, cesium chloride centrifugation gradients, or by any other means known to one of ordinary skill in the art (see for example, Sambrook et al. 2000). The nucleic acid molecule is preferably isolated, which means that it is essentially free of other nucleic acids. Essentially free from other nucleic acids means that the nucleic acid molecule is at least about 90%, preferably at least about 95% and, more preferably at least about 98% free of other nucleic acids. Preferably, the molecule is essentially pure, which means that the molecule is free not only of other nucleic acids, but also of other materials used in the synthesis and isolation of the molecule. Materials used in synthesis include, for example, enzymes. Materials used in isolation include, for example, gels, such as SDS-PAGE. The molecule is at least about 90% free, preferably at least about 95% free and, more preferably at least about 98% free of other nucleic acids and such other materials.

For example, when the level of expression of said gene(s) is determined by detecting a translation product of said gene, the translation product is a polypeptide of sequence SEQ ID NO : 2 ; SEQ ID NO : 5 ; SEQ ID NO : 7 ; SEQ ID NO : 9 ; SEQ ID NO

1 1 SEQ ID NO 13 ; SEQ ID NO : 15 ; SEQ ID NO 17 SEQ ID NO 20 ; SEQ ID NO :

22 SEQ ID NO 24 ; SEQ ID NO : 26 ; SEQ ID NO 28 SEQ ID NO 30 ; SEQ ID NO :

32 SEQ ID NO 34 ; SEQ ID NO : 36 ; SEQ ID NO 38 SEQ ID NO 40 ; SEQ ID NO :

42 SEQ ID NO 44 ; SEQ ID NO : 46 ; SEQ ID NO 48 SEQ ID NO 50 ; SEQ ID NO :

52 SEQ ID NO 54 ; SEQ ID NO : 56 ; SEQ ID NO 58 SEQ ID NO 60 ; SEQ ID NO :

62 ; SEQ ID NO : 64 ; SEQ ID NO : 67 ; or a variant or fragment thereof. Preferably, the translation product is at least 1 , 2, 3, 4 polypeptide(s) of sequence SEQ ID NO : 2; SEQ ID NO : 5; SEQ ID NO : 13; SEQ ID NO : 30 ; or a variant or fragment thereof.

As used herein the term "polypeptide" refers to any chain of amino acids linked by peptide bonds, regardless of length or post-translational modification. Polypeptides include natural proteins, synthetic or recombinant polypeptides and peptides (i.e. polypeptides of less than 50 amino acids) as well as hybrid, post-translationally modified polypeptides, and peptidomimetic.

As used herein, the term "amino acid" refers to the 20 standard alpha-amino acids as well as naturally occurring and synthetic derivatives. A polypeptide may contain L or D amino acids or a combination thereof.

The term "variants" includes protein and nucleic acid variants. Variant proteins may be naturally occurring variants, such as splice variants, alleles and isoforms, or they may be produced by recombinant means. Variations in amino acid sequence may be introduced by substitution, deletion or insertion of one or more codons into the nucleic acid sequence encoding the protein that results in a change in the amino acid sequence of the protein. Optionally the variation is by substitution of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids with any other amino acid in the protein. Amino acid substitutions may be conservative or non-conservative. Preferably, substitutions are conservative substitutions, in which one amino acid is substituted for another amino acid with similar structural and/or chemical properties. Additionally or alternatively, the variation may be by addition or deletion of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids within the protein.

Amino acid substitutions may be conservative or non-conservative. Preferably, substitutions are conservative substitutions, in which one amino acid is substituted for another amino acid with similar structural and/or chemical properties. Exemplary conservative substitutions are listed below.

Ala (A) val; leu; ile

Arg (R) lys; gin; asn

Asn (N) gin; his; lys

Asp (D) glu

Cys (C) ser

Gin (Q) asn

Glu (E) asp

Gly (G) pro; ala

His (H) asn; Gin; lys; arg

He (I) leu; val; met; ala

norleucine leu

Leu (L) norleucine; ile; met; ala; phe

Lys (K) arg; Gin; asn

Met (M) leu; phe; ile

Phe (F) leu; val; ile; ala; tyr

Pro (P) ala

Ser (S) thr

Thr (T) ser

Trp (W) tyr; phe

Tyr (Y) trp; phe; thr; ser

Val (V) ile; leu; met; phe; ala; norleucine Variant proteins may include proteins that have at least about 80% amino acid sequence identity with a polypeptide sequence disclosed herein. Preferably, a variant protein will have at least about 80%, 81 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% amino acid sequence identity to a full-length polypeptide sequence or a fragment of a polypeptide sequence as disclosed herein. Amino acid sequence identity is defined as the percentage of amino acid residues in the variant sequence that are identical with the amino acid residues in the reference sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Sequence identity may be determined over the full length of the variant sequence, the full length of the reference sequence, or both. Methods for sequence alignment and determination of sequence identity are well known in the art, for example using publicly available computer software such as BioPerl, BLAST, BLAST-2, CS-BLAST, FASTA, ALIGN, ALIGN-2, LALIGN, Jaligner, matcher or Megalign (DNASTAR) software and alignment algorithms such as the Needleman-Wunsch and Smith-Waterman algorithms. The percentage of identity may be calculated by performing a pairwise global alignment based on the Needleman-Wunsch alignment algorithm to find the optimum alignment (including gaps) of two sequences along their entire length, for instance using Needle, and using the BLOSUM62 matrix with a gap opening penalty of 10 and a gap extension penalty of 0.5.

For example, the percentage identity may be calculated by performing a pairwise global alignment based on the Needleman-Wunsch alignment algorithm to find the optimum alignment (including gaps) of two sequences along their entire length, for instance using Needle, and using the BLOSUM62 matrix with a gap opening penalty of 10 and a gap extension penalty of 0.5.

Fragments of the proteins and variant proteins disclosed herein are also encompassed by the invention. Such fragments may be truncated at the N-terminus or C- terminus, or may lack internal residues, for example, when compared with a full length protein. Certain fragments lack amino acid residues that are not essential for enzymatic activity. Preferably, said fragments are at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 1 10, 120, 150, 250, 300, 350, 400, 450, 500 or more amino acids in length.

Variant nucleic acid sequences include sequences capable of specifically hybridizing to the sequence of SEQ ID NO : 1 ; SEQ ID NO : 3; SEQ ID NO : 4; SEQ ID NO : 6; SEQ ID NO : 8; SEQ ID NO : 10; SEQ ID NO : 12; SEQ ID NO : 14; SEQ ID NO : 16; SEQ ID NO : 18; SEQ ID NO : 19; SEQ ID NO : 21 ; SEQ ID NO : 23; SEQ ID NO : 25 SEQ ID NO : 27 SEQ ID NO : 29 SEQ ID NO : 31 SEQ ID NO : 33 SEQ ID NO : 35 SEQ ID NO : 37 SEQ ID NO : 39 SEQ ID NO : 41 SEQ ID NO : 43 SEQ ID NO : 45 SEQ ID NO : 47 SEQ ID NO : 49 SEQ ID NO : 51 SEQ ID NO : 53 SEQ ID NO : 55 SEQ ID NO : 57 SEQ ID NO : 59 SEQ ID NO : 61 SEQ ID NO : 63 SEQ ID NO : 65 SEQ ID NO : 66; under moderate or high stringency conditions. Stringent conditions or high stringency conditions may be identified by those that: (1 ) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1 % sodium dodecyl sulfate at 50 °C; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1 % bovine serum albumin/0.1 % Ficoll/0.1 % polyvinylpyrrolidone/5 OmM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42 °C; or (3) employ 50% formamide, 5 x SSC (0.75 M NaCI, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1 % sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 Mg/ml), 0.1 % SDS, and 10% dextran sulfate at 42 ^< C, with washes at 42 ^< C in 0.2 x SSC (sodium chloride/sodium citrate) and 50% formamide at 55°C, followed by a high-stringency wash consisting of 0.1 x SSC containing EDTA at 55 °C. Moderately stringent conditions may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37°C in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCI, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50 ^.

Variant nucleic acid sequences may include nucleic acid sequences that have at least about 80% nucleic acid sequence identity with a nucleic acid sequence disclosed herein. Preferably, a variant nucleic acid sequence will have at least about 80%, 81 %, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% nucleic acid sequence identity to a full-length nucleic acid sequence or a fragment of a nucleic acid sequence as disclosed herein. Nucleic acid sequence identity can be calculated by methods well-known to one of skill in the art. The percentage of identity may be calculated by performing a pairwise global alignment based on the Needleman-Wunsch alignment algorithm to find the optimum alignment (including gaps) of two sequences along their entire length, for instance using Needle, and using the BLOSUM62 matrix with a gap opening penalty of 10 and a gap extension penalty of 0.5. In one embodiment, the method for predicting whether a cancer patient will respond to therapy additionally comprises the steps of:

(a) comparing the level of expression of said gene with that of a control sample

(b) predicting whether said patient will respond to said therapy based on comparison with the control sample.

By comparing the level of expression of at least one gene of table 1 in the patient biological sample to the one of a control sample, an alteration of the expression of said gene(s) or a similar level of expression may be detected.

The term "similar level of expression" as used herein means that there is no or little difference in the level of expression of at least one gene of table 1 between a first sample as compared with a second sample (such as a control sample). There is a similar level of expression of at least one gene of table 1 between two samples when there is no statistically significant difference in the level of expression of said genes.

An alteration of the expression of at least one gene of table 1 by comparing its level of expression in the patient biological sample to the one of a control sample is indicative that the patient is sensitive or resistant to therapy.

The "alteration of the expression" a gene of table 1 refers to a statistically significant difference in the level of expression of said gene measured between two samples such as for example, the patient biological sample and the control sample. In one embodiment, the alteration of the expression can be compared using the ratio of the level of expression of a given gene or gene(s) as compared with the expression level of the given gene or gene(s) of another sample, wherein the ratio is not equal to 1 . For example, there is an alteration of the expression of a gene if the ratio of the level of expression in a first sample as compared with a second sample is greater than or less than 1 .0. For example, a ratio of greater than 1 , 1 .2, 1 .5, 1 .7, 2, 3, 3, 5, 10, 15, 20 or more, or a ratio less than 1 , 0.8, 0.6, 0.4, 0.2, 0.1 0.05, 0.001 or less. In another embodiment the alteration of the expression is measured using p-value. For instance, when using p-value, an alteration of the expression of a gene is as between a first sample and a second sample or a control sample when the p-value is less than 0.1 , preferably less than 0.05, more preferably less than 0.01 , even more preferably less than 0.005, the most preferably less than 0.001 . In one embodiment, the "alteration of the expression" means an increase (over-expression) or a decrease (under-expression) of the level of expression of a gene of table 1 by comparing its level of expression between two samples such as for example, by comparing a biological sample of a patient to a control sample. In some embodiment, the under-expression of at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17 gene(s) selected from the group consisting of PLOD2; MRPS16; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; JAK1 ; APOL6; ST8SIA4; ITGA4; PPIF; CSPP1 ; HAVCR2; TRD@; TAP2 or one variant thereof, and preferably, PLOD2 and/or JAK1 or one variant thereof, compared to the control sample is indicative of a patient that does not respond or has reduced response to a therapy wherein the control sample is a biological sample of a cancer patient or a group of cancer patients that responds to said therapy and/or a healthy subject or a group of healthy subjects.

In some embodiment, the over-expression of at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17 gene(s) selected from the group consisting of PLOD2; MRPS16; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; JAK1 ; APOL6; ST8SIA4; ITGA4; PPIF; CSPP1 ; HAVCR2; TRD@; TAP2 or one variant thereof, and preferably, PLOD2 and/or JAK1 or one variant thereof ,compared to the control sample is indicative of a patient that responds to therapy wherein the control sample is a biological sample of a cancer patient or a group of cancer patients that does not respond or has reduced response to said therapy.

In some embodiment, the over-expression of at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 gene(s) selected from the group consisting of H19 ;SIX1 ; PCDHA1 ; S100A1 ; TK2; PCDHB15; VGLL4; CCNO; PCDHB14; PCDHB18; RHOU ; TMEM63A; RPS6KL1 ; FUT6; SIDT2 ; C5orf4 ; CES3; C14orf39 or one variant thereof, and preferably, SIX1 and/or TK2 or one variant thereof, compared to the control sample is indicative of a patient that does not respond or has reduced response to a therapy wherein the control sample is a biological sample of a cancer patient or a group of cancer patients that responds to said therapy, and/or a healthy subject or a group of healthy subjects.

In some embodiment, the under-expression of at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 ,

12, 13, 14, 15, 16, 17, 18, 19, 20 gene(s) selected from the group consisting of H19 ;SIX1 ;

S100A1 ; TK2; PCDHB15; VGLL4; CCNO; PCDHA1 ; PCDHB14; PCDHB18; RHOU ;

TMEM63A; RPS6KL1 ; FUT6; SIDT2 ; C5orf4 ; CES3; C14orf39 or one variant thereof and preferably, SIX1 and/or TK2 or one variant thereof, compared to the control sample is indicative of a patient that responds to therapy wherein the control sample is a biological sample of a cancer patient or a group of cancer patients that does not respond or has reduced response to said therapy.

According to the invention, when the method of the invention involves comparing the level of expression of a gene of table 1 with that of a control sample obtained from an individual (healthy subject or cancer patients) or a group of individuals (a group of healthy subjects or a group of cancer patients), the level of expression of said gene in said control sample is called a "control value". The control value can be any number of statistical measures to distinguish therapy-sensitive and/or therapy-resistant levels, including Mean and Median expression levels, and/or cut-off or threshold gene expression or fold change values as determined in an individual or a group of individuals. The control values for at least 2, 3 or 4 genes selected from the group consisting of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; IF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 or one variant thereof define a gene expression signature. Preferably, the control values for at least 2, 3 or 4 genes selected from the group consisting of PLOD2; SIX1 ; TK2; JAK1 or one variant thereof define a gene expression signature.

For example, the control values for at least 2, 3 or 4 genes selected from the group consisting of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; IF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 or one variant thereof as determined in a biological sample from a cancer patient or a group of cancer patients that responds to therapy define a therapy-resistant gene expression signature or a therapy-sensitive gene expression signature. As further example, the control values for at least 2, 3 or 4 genes selected from the group consisting of PLOD2; SIX1 ; TK2; JAK1 or one variant thereof as determined in a biological sample from a cancer patient or a group of cancer patients that responds to therapy define a therapy- resistant gene expression signature or a therapy-sensitive gene expression signature.

For predicting the sensitivity or the resistance of a patient to therapy, a cancer patient is evaluated for the presence of one or more of the gene of table 1 , by scoring or classifying the patient expression level against the gene expression signature (therapy- sensitive gene expression signature or therapy-resistant gene expression signature). Various classification schemes are known for classifying samples between two or more classes or groups, and these include, without limitation: Principal Components Analysis, Naive Bayes, Support Vector Machines, Nearest Neighbors, Decision Trees, Logistic, Artificial Neural Networks, and Rule-based schemes. In addition, the predictions from multiple models can be combined to generate an overall prediction.

The control sample is a biological sample obtained from an individual or a group of individuals. A "biological sample" encompasses a variety of sample types obtained from an individual and can be used in a diagnostic or monitoring assay. The definition encompasses a clinical sample, solid tissue samples such as a biopsy specimen or tissue cultures, cells in culture, cell supernatants, cell lysates or cells derived there from and the progeny thereof, and also includes serum, plasma, blood and other liquid samples of biological origin. The definition also includes samples that have been manipulated in any way after their procurement, such as by treatment with reagents, solubilization, purification or enrichment for certain components, such as polypeptides or nucleic acids.

When the control sample is a biological sample from "a healthy subject" "a group of healthy subjects", the expression "healthy subject(s)" refers an individual or a reference group of individuals who are not suffering from or who did not develop a cancer.

When the control sample is a biological sample from "a cancer patient or a group of cancer patients that does not respond or has reduced response to said therapy" an individual or a reference group of individuals who are suffering from or who developed a cancer and have been diagnosed as resistant or as having reduced response to a therapy.

When the control sample is a biological sample from "a cancer patient or a group of cancer patients that responds to said therapy" an individual or a reference group of individuals who are suffering from or who developed a cancer and have been diagnosed as sensitive to a therapy.

After comparing the patient's gene(s) level of expression to the gene expression signature, therapy-sensitive and/or therapy-resistant signature, the sample is classified as, or for example, given a probability of being, a therapy-sensitive patient or a therapy- resistant patient. The classification may be determined computationally based upon known methods as described above. The result of the computation may be displayed on a computer screen or presented in a tangible form, for example, as a probability (e.g., from 0 to 100%) of the patient responding to said therapy. In various embodiments, the method according the invention distinguishes a therapy-sensitive tumor from a therapy-resistant tumor with at least about 60%, 75%, 80%, 85%, 90% or greater accuracy.

The invention further relates to a method of monitoring efficiency of cancer therapy comprising:

a) determining the expression level of at least one gene selected from the group consisting of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75;

CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6;

ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18;PPIF; RHOU; TMEM63A; RPS6KL1 ;

CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 in a biological sample from a patient undergoing said therapy, b) repeating step a) on another biological sample from the same patient taken at a later point in time;

wherein said therapy preferably comprises a treatment with a taxane, and

wherein an alteration of the expression level of said gene(s) is indicative of the efficacy of said therapy.

Typically, said method comprises determining the level of expression of at least PLOD2 and TK2; or at least PLOD2 and SIX1 ; or at least PLOD2 and JAK1 ; or at least TK2 and SIX1 ; or at least TK2 and JAK1 ; or at least SIX1 and JAK1 ; or at least SIX1 ; PLOD2 and TK2; or at least SIX1 , PLOD2 and JAK1 ; or at least SIX1 , TK2 and JAK1 ; or at least TK2, PLOD2 and JAK1 ; or at least SIX1 , PLOD2; TK2 and JAK1 ; or PLOD2, JAK1 and H19; or at least PLOD2, SIX1 and JAK1 ; or at least PLOD2, SIX1 and PCDHA1 ; or at least PLOD2, SIX1 and S100A1 ; or at least PLOD2, JAK1 and MRPS16; or at least PLOD2, SIX1 and TK2; or at least PLOD2, SIX1 and C8orf75; or at least PLOD2, SIX1 and CDH4; or at least PLOD2, SIX1 and LOC100131756; or at least PLOD2, SIX1 and ZC3H12B; or at least PLOD2, SIX1 and CHAC2; or at least PLOD2, JAK1 and EIF2AK2; or at least PLOD2, SIX1 and PCDHB15; or at least PLOD2, SIX1 and VGLL4; or at least PLOD2, RHOU and SIX1 ; or at least PLOD2, SIX1 and APOL6; or at least PLOD2, JAKI and ST8SIA4; or at least PLOD2, SIX1 and CCNO; or at least PLOD2, JAK1 and PCDHB14; or at least PLOD2, SIX1 and ITGA4; or at least PLOD2, JAK1 and PCDHB18; or at least PLOD2, SIX1 and PPIF; or at least PLOD2, SIX1 and TMEM63A; or at least PLOD2, SIX1 and RPS6KL1 ; or at least PLOD2, RHOU and CSPP1 ; or at least PLOD2, SIX1 and FUT6; or at least PLOD2, SIX1 and SIDT2; or at least PLOD2, SIX1 and HAVCR2; or at least PLOD2, SIX1 and C5orf4; or at least PLOD2, SIX1 and CES3; or at least PLOD2, SIX1 and C14orf39; or at least PLOD2, SIX1 and TRD@; or at least PLOD2, SIX1 and TAP2 in a biological sample from a patient undergoing said therapy.

In one embodiment, the "alteration of the expression" means an increase or a decrease of the level of expression of a gene by comparing its level of expression in a biological sample of the patient following treatment with the therapy to its level of expression in a biological sample of the patient prior to treatment with the therapy:

(i) wherein a decrease above a control value in the level of expression of at least

1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 gene(s) selected from the group consisting of H19 ;SIX1 ; PCDHA1 ; S100A1 ; TK2; PCDHB15; VGLL4; CCNO; PCDHB14; PCDHB18; RHOU ; TMEM63A; RPS6KL1 ; FUT6; SIDT2 ; C5orf4 ; CES3; C14orf39 following treatment with the therapy relative to the level of expression of said gene(s) prior treatment with the therapy indicates that the therapy is efficient for treating the patient; typically, wherein a decrease above a control value in the level of expression of at least SIX1 and H19; or SIX1 and PCDHA1 ; or RHOU and S100A1 ; or H19 and TK2; or H19 and PCDHB15; or H19 and VGLL4; or H19 and CCNO; or H19 and PCDHB14; or H19 and PCDHB18; or H19 and RHOU; or H19 and TMEM63A; or H19 and RPS6KL1 ; or H19 and FUT6; or H19 and SIDT2; or H19 and C5orf4; or H19 and CES3; or H19 and C14orf39; or SIX1 and PCDHA1 ; or SIX1 and S100A1 ; or SIX1 and TK2; or SIX1 and PCDHB15; or SIX1 and VGLL4; or SIX1 and CCNO; or SIX1 and PCDHB14; or SIX1 and PCDHB18; or SIX1 and RHOU; or SIX1 and TMEM63A; or SIX1 and RPS6KL1 ; or SIX1 and FUT6; or SIX1 and SIDT2; or SIX1 and C5orf4; or SIX1 and CES3; or SIX1 and C14orf39, or SIX1 , TK2 and S100A1 ; or SIX1 , TK2 and PCDHB15; or SIX1 , TK2 and VGLL4; or SIX1 , TK2 and CCNO; or SIX1 , TK2 and PCDHB14; or SIX1 , TK2 and PCDHB18; or SIX1 , TK2 and TMEM63A; or SIX1 , TK2 and RPS6KL1 ; or SIX1 , TK2 and FUT6; or SIX1 , TK2 and SIDT2; or SIX1 , TK2 and C5orf4; or SIX1 , TK2 and CES3; or SIX1 , TK2 and C14orf39, or TK2 and PCDHA1 ; or TK2 and S100A1 ; or SIX1 and/or TK2; or TK2 and PCDHB15; or TK2 and VGLL4; or TK2 and CCNO; or RHOU and PCDHB14; or TK2 and PCDHB18; or TK2 and TMEM63A; or TK2 and RPS6KL1 ; or TK2 and FUT6; or TK2 and SIDT2; or TK2 and C5orf4; or TK2 and CES3; or TK2 and C14orf39 following treatment with the therapy relative to the level of expression of said gene(s) prior treatment with the therapy indicates that the therapy is efficient for treating the patient or (ii) wherein an increase above a control value in the level of expression of at least

1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17 gene(s) selected from the group consisting of PLOD2; MRPS16; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; JAK1 ; APOL6; ST8SIA4; ITGA4; PPIF; CSPP1 ; HAVCR2; TRD@; TAP2 following treatment with the therapy relative to the level of expression of said gene(s) prior to treatment with the therapy indicates that the therapy is efficient for treating the patient, typically, wherein an increase above a control value in the level of expression of at least PLOD2 and MRPS16; or PLOD2 and C8orf75; or PLOD2 and CDH4; or PLOD2 and LOC100131756; or PLOD2 and ZC3H12B; or PLOD2 and CHAC2; or PLOD2 and EIF2AK2; or PLOD2 and/or JAK1 ; or PLOD2 and APOL6; or PLOD2 and ST8SIA4; or PLOD2 and ITGA4; or PLOD2 and PPIF; or PLOD2 and CSPP1 ; or PLOD2 and HAVCR2; or PLOD2 and TRD@; or PLOD2 and TAP2 or JAK1 and C8orf75; or JAK1 and CDH4; or JAK1 and LOC100131756; or JAK1 and ZC3H12B; or JAK1 and CHAC2; or JAK1 and EIF2AK2; or MRPS16 and JAK1 ; or JAK1 and APOL6; or JAK1 and ST8SIA4; or JAK1 and ITGA4; or JAK1 and PPIF; or JAK1 and CSPP1 ; or JAK1 and HAVCR2; or JAK1 and TRD@; or JAK1 and TAP2 or PLOD2, JAK1 and CDH4; or PLOD2, JAK1 and LOC100131756; or PLOD2, JAK1 and ZC3H12B; or PLOD2, JAK1 and CHAC2; or PLOD2, JAK1 and EIF2AK2; or PLOD2, JAK1 and JAK1 ; or PLOD2, JAK1 and APOL6; or PLOD2, JAK1 and ST8SIA4; or PLOD2, JAK1 and ITGA4; or PLOD2, JAK1 and PPIF; or PLOD2, JAK1 and CSPP1 ; or PLOD2, JAK1 and HAVCR2; or PLOD2, JAK1 and TRD@; or PLOD2, JAK1 and TAP2; or PLOD2, JAK1 and MRPS16; or PLOD2, JAK1 and C8orf75; or PLOD2, JAK1 and LOC100131756; or CDH4 and ZC3H12B; or CDH4 and CHAC2; or CDH4 and EIF2AK2; or or CDH4 and APOL6; or CDH4 and ST8SIA4; or CDH4 and ITGA4; or CDH4 and PPIF; or CDH4 and CSPP1 ; or CDH4 and HAVCR2; or CDH4 and TRD@; or CDH4 and TAP2; or LOC100131756 and CDH4; or LOC100131756 and ZC3H12B; or LOC100131756 and CHAC2; or LOC100131756 and EIF2AK2; or LOC100131756 and APOL6; or LOC100131756 and ST8SIA4; or LOC100131756 and ITGA4; or LOC100131756 and PPIF; or LOC100131756 and CSPP1 ; or LOC100131756 and HAVCR2; or LOC100131756 and TRD@; or LOC100131756 and TAP2 following treatment with the therapy relative to the level of expression of said gene(s) prior to treatment with the therapy indicates that the therapy is efficient for treating the patient or (iii) wherein an increase above a control value in the level of expression of at least

1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20 gene(s) selected from the group consisting of H19 ;SIX1 ; PCDHA1 ; S100A1 ; TK2; PCDHB15; VGLL4; CCNO; PCDHB14; PCDHB18; RHOU ; TMEM63A; RPS6KL1 ; FUT6; SIDT2 ; C5orf4 ; CES3; C14orf39 following treatment with the therapy relative to the level of expression of said gene(s) prior to treatment with the therapy indicates that the therapy is not efficient for treating the patient; typically, wherein an increase above a control value in the level of expression of at least SIX1 and H19; or SIX1 and PCDHA1 ; or RHOU and S100A1 ; or H19 and TK2; or H19 and PCDHB15; or H19 and VGLL4; or H19 and CCNO; or H19 and PCDHB14; or H19 and PCDHB18; or H19 and RHOU; or H19 and TMEM63A; or H19 and RPS6KL1 ; or H19 and FUT6; or H19 and SIDT2; or H19 and C5orf4; or H19 and CES3; or H19 and C14orf39; or SIXI and PCDHA1 ; or SIX1 and S100A1 ; or SIX1 and TK2; or SIX1 and PCDHB15; or SIX1 and VGLL4; or SIX1 and CCNO; or SIX1 and PCDHB14; or SIX1 and PCDHB18; or SIX1 and RHOU; or SIX1 and TMEM63A; or SIX1 and RPS6KL1 ; or SIX1 and FUT6; or SIX1 and SIDT2; or SIX1 and C5orf4; or SIX1 and CES3; or SIX1 and C14orf39, or SIX1 , TK2 and S100A1 ; or SIX1 , TK2 and PCDHB15; or SIX1 , TK2 and VGLL4; or SIX1 , TK2 and CCNO; or SIX1 , TK2 and PCDHB14; or SIX1 , TK2 and PCDHB18; or SIX1 , TK2 and TMEM63A; or SIX1 , TK2 and RPS6KL1 ; or SIX1 , TK2 and FUT6; or SIX1 , TK2 and SIDT2; or SIX1 , TK2 and C5orf4; or SIX1 , TK2 and CES3; or SIX1 , TK2 and C14orf39, or TK2 and PCDHA1 ; or TK2 and S100A1 ; or SIX1 and/or TK2; or TK2 and PCDHB15; or TK2 and VGLL4; or TK2 and CCNO; or RHOU and PCDHB14; or TK2 and PCDHB18; or TK2 and TMEM63A; or TK2 and RPS6KL1 ; or TK2 and FUT6; or TK2 and SIDT2; or TK2 and C5orf4; or TK2 and CES3; or TK2 and C14orf39 following treatment with the therapy relative to the level of expression of said gene(s) prior to treatment with the therapy indicates that the therapy is not efficient for treating the patient or

(iv) wherein a decrease above a control value in the level of expression of at least

1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17 gene(s) selected from the group consisting of PLOD2; MRPS16; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; JAK1 ; APOL6; ST8SIA4; ITGA4; PPIF; CSPP1 ; HAVCR2; TRD@; TAP2 following treatment with the therapy relative to the level of expression of said gene(s) prior to treatment with the therapy, indicates that the therapy is not efficient for treating the patient; wherein a decrease above a control value in the level of expression of at least PLOD2 and MRPS16; or PLOD2 and C8orf75; or PLOD2 and CDH4; or PLOD2 and LOC100131756; or PLOD2 and ZC3H12B; or PLOD2 and CHAC2; or PLOD2 and EIF2AK2; or PLOD2 and/or JAK1 ; or PLOD2 and APOL6; or PLOD2 and ST8SIA4; or PLOD2 and ITGA4; or PLOD2 and PPIF; or PLOD2 and CSPP1 ; or PLOD2 and HAVCR2; or PLOD2 and TRD@; or PLOD2 and TAP2 or JAK1 and C8orf75; or JAK1 and CDH4; or JAK1 and LOC100131756; or JAK1 and ZC3H12B; or JAK1 and CHAC2; or JAK1 and EIF2AK2; or MRPS16 and JAK1 ; or JAK1 and APOL6; or JAK1 and ST8SIA4; or JAK1 and ITGA4; or JAK1 and PPIF; or JAK1 and CSPP1 ; or JAK1 and HAVCR2; or JAK1 and TRD@; or JAK1 and TAP2 or PLOD2, JAK1 and CDH4; or PLOD2, JAK1 and LOC100131756; or PLOD2, JAK1 and ZC3H12B; or PLOD2, JAK1 and CHAC2; or PLOD2, JAK1 and EIF2AK2; or PLOD2, JAK1 and JAK1 ; or PLOD2, JAK1 and APOL6; or PLOD2, JAK1 and ST8SIA4; or PLOD2, JAK1 and ITGA4; or PLOD2, JAK1 and PPIF; or PLOD2, JAK1 and CSPP1 ; or PLOD2, JAK1 and HAVCR2; or PLOD2, JAK1 and TRD@; or PLOD2, JAK1 and TAP2; or PLOD2, JAK1 and MRPS16; or PLOD2, JAK1 and C8orf75; or PLOD2, JAK1 and LOC100131756; or CDH4 and ZC3H12B; or CDH4 and CHAC2; or CDH4 and EIF2AK2; or or CDH4 and APOL6; or CDH4 and ST8SIA4; or CDH4 and ITGA4; or CDH4 and PPIF; or CDH4 and CSPP1 ; or CDH4 and HAVCR2; or CDH4 and TRD@; or CDH4 and TAP2; or LOC100131756 and CDH4; or LOC100131756 and ZC3H12B; or LOC100131756 and CHAC2; or LOC100131756 and EIF2AK2; or LOC100131756 and APOL6; or LOC100131756 and ST8SIA4; or LOC100131756 and ITGA4; or LOC100131756 and PPIF; or LOC100131756 and CSPP1 ; or LOC100131756 and HAVCR2; or LOC100131756 and TRD@; or LOC100131756 and TAP2 following treatment with the therapy relative to the level of expression of said gene(s) prior to treatment with the therapy, indicates that the therapy is not efficient for treating the patient or (v) wherein when a level of expression of at least 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35genes selected from the group consisting of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; IF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 or one variant thereof following treatment with the therapy is identical or similar or changed below a control value as compared to prior to treatment with the therapy then the treatment is not efficient for treating the patient, typically, wherein when a level of expression of PLOD2 and TK2; or at least PLOD2 and SIX1 ; or at least PLOD2 and JAK1 ; or at least TK2 and SIX1 ; or at least TK2 and JAK1 ; or at least SIX1 and JAK1 ; or at least SIX1 ; PLOD2 and TK2; or at least SIX1 , PLOD2 and JAK1 ; or at least SIX1 , TK2 and JAK1 ; or at least TK2, PLOD2 and JAK1 ; or at least SIX1 , PLOD2; TK2 and JAK1 ; or at least PLOD2, JAK1 and H19; or at least PLOD2, JAKI and SIX1 ; or at least PLOD2, JAK1 and PCDHA1 ; or at least PLOD2, JAKI and S100A1 ; or at least PLOD2, JAK1 and MRPS16; or at least PLOD2, JAKI and TK2; or at least PLOD2, JAK1 and C8orf75; or at least PLOD2, JAK1 and CDH4; or at least PLOD2, JAK1 and LOC100131756; or at least PLOD2, JAK1 and ZC3H12B; or at least PLOD2, JAK1 and CHAC2; or at least PLOD2, JAK1 and EIF2AK2; or at least PLOD2, JAK1 and PCDHB15; or at least PLOD2, JAK1 and VGLL4; or at least PLOD2, RHOU and JAK1 ; or at least PLOD2, JAK1 and APOL6; or at least PLOD2, JAK1 and ST8SIA4; or at least PLOD2, JAK1 and CCNO; or at least PLOD2, JAK1 and PCDHB14; or at least PLOD2, JAK1 and ITGA4; or at least PLOD2, JAK1 and PCDHB18; or at least PLOD2, JAK1 and PPIF; or at least PLOD2, JAK1 and TMEM63A; or at least PLOD2, JAK1 and RPS6KL1 ; or at least PLOD2, JAK1 and CSPP1 ; or at least PLOD2, JAK1 and FUT6; or at least PLOD2, JAK1 and SIDT2; or at least PLOD2, JAK1 and HAVCR2; or at least PLOD2, JAK1 and C5orf4; or at least PLOD2, JAK1 and CES3; or at least PLOD2, JAK1 and C14orf39; or at least PLOD2, JAK1 and TRD@; or at least PLOD2, JAK1 and TAP2 or one variant thereof following treatment with the therapy is identical or similar or changed below a control value as compared to prior to treatment with the therapy then the treatment is not efficient for treating the patient.

The method according to the invention will aid a physician in selecting a course of treatment for the cancer patient. For example, in certain embodiments of the invention, the patient will be determined to be a therapy-sensitive patient on the basis of a probability, and the patient will be subsequently treated with that therapy alone in combination with other chemotherapeutic drugs. In other embodiments, the patient will be determined to be therapy-resistant, thereby allowing the physician to exclude that candidate treatment for the patient, thereby sparing the patient the unnecessary toxicity.

Indeed, the invention concerns, a method for determining a therapeutic regimen suitable for treating a subject suffering from a cancer, wherein said method comprises the steps of:

a) predicting whether said patient will respond to a therapy using the method for predicting whether a cancer patient will respond to therapy according to the invention, and b) deducing a suitable therapeutic regimen for the subject.

Further provided is a method of prognosing or classifying the outcome of cancer in a patient undergoing a therapy comprising a treatment with a taxane, said method comprises the step of determining the level of expression of at least one gene selected from the group consisting of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2;

C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4;

JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2 in a biological sample from the patient.

Typically, said method comprises determining the level of expression of PLOD2 and TK2; or at least PLOD2 and SIX1 ; or at least PLOD2 and JAK1 ; or at least TK2 and SIX1 ; or at least TK2 and JAK1 ; or at least SIX1 and JAK1 ; or at least SIX1 ; PLOD2 and TK2; or at least SIX1 , PLOD2 and JAK1 ; or at least SIX1 , TK2 and JAK1 ; or at least TK2, PLOD2 and JAK1 ; or at least SIX1 , PLOD2; TK2 and JAK1 ; or at least PLOD2, JAK1 and H19; or at least PLOD2, SIX1 and JAK1 ; or at least PLOD2, SIX1 and PCDHA1 ; or at least PLOD2, SIX1 and S100A1 ; or at least PLOD2, JAK1 and MRPS16; or at least PLOD2, SIX1 and TK2; or at least PLOD2, SIX1 and C8orf75; or at least PLOD2, SIX1 and CDH4; or at least PLOD2, SIX1 and LOC100131756; or at least PLOD2, SIX1 and ZC3H12B; or at least PLOD2, SIX1 and CHAC2; or at least PLOD2, JAK1 and EIF2AK2; or at least PLOD2, SIX1 and PCDHB15; or at least PLOD2, SIX1 and VGLL4; or at least PLOD2, RHOU and SIX1 ; or at least PLOD2, SIX1 and APOL6; or at least PLOD2, JAKI and ST8SIA4; or at least PLOD2, SIX1 and CCNO; or at least PLOD2, JAK1 and PCDHB14; or at least PLOD2, SIX1 and ITGA4; or at least PLOD2, JAK1 and PCDHB18; or at least PLOD2, SIX1 and PPIF; or at least PLOD2, SIX1 and TMEM63A; or at least PLOD2, SIX1 and RPS6KL1 ; or at least PLOD2, RHOU and CSPP1 ; or at least PLOD2, SIX1 and FUT6; or at least PLOD2, SIX1 and SIDT2; or at least PLOD2, SIX1 and HAVCR2; or at least PLOD2, SIX1 and C5orf4; or at least PLOD2, SIX1 and CES3; or at least PLOD2, SIX1 and C14orf39; or at least PLOD2, SIX1 and TRD@; or at least PLOD2, SIX1 and TAP2 in a biological sample from the patient The terms "cancer" and "cancerous" refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer is lung, breast, brain, prostate, spleen, pancreatic, cervical, ovarian, head and neck, esophageal, liver, skin, kidney, leukemia, bone, testicular, colon, or bladder cancer.

The term "prognosing" is used herein to refer to the prediction of the likelihood of benefit from therapy. The term "prediction" or "predicting" refers to the likelihood that a patient will respond either favourably or unfavourably to a particular therapy. In one embodiment, prediction or predicting relates to the extent of those responses. In one embodiment, the prediction or predicting relates to whether and/or the probability that a patient will survive or improve following treatment, for example treatment with a particular therapeutic agent, and for a certain period of time without disease recurrence. The predictive methods of the invention can be used clinically to make treatment decisions by choosing the most appropriate treatment modalities for any particular patient. The predictive methods of the present invention are valuable tools in predicting if a patient is likely to respond favourably to a treatment regimen, such as a given therapeutic regimen, or whether long-term survival of the patient following a therapeutic regimen is likely.

The term "therapy "or "therapeutic regimen" refers to a course of treatment intended to reduce or eliminate the affects or symptoms of a disease or to prevent progression of a disease from one state to a second, more detrimental state. A therapeutic regimen can comprise a prescribed drug, surgery or radiation treatment.

In the context of the present invention, the individual or patient is preferably a human individual. The individual may thus also correspond to a non-human individual, preferably a non-human mammal such as a rodent, a feline, a canine, or a primate.

The invention concerns a panel of cancer therapy markers, said panel comprising or consisting of at least one marker selected from the group consisting of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2.

The term "marker" in the expression "cancer therapy markers" means a distinctive biological or biologically-derived indicator of a process, event, or condition. The term marker as used herein refers to a gene that is differentially expressed in individuals with cancer such as breast cancer, according to their sensitivity or resistance to therapy and notably taxanes The marker according to the invention is suitable to be used in methods of diagnosis (e.g. clinical screening), prognosis assessment; in monitoring the results of therapy, identifying patients most likely to respond to a particular therapeutic treatment, drug screening and development. Preferably, the marker is a gene, mRNA, a protein or peptide or variant of PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; ST8SIA4; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2. Markers and uses thereof are valuable for identification of new drug treatments and for discovery of new targets for drug treatment.

Typically, said panel comprises or consists of at least PLOD2 and TK2; or at least PLOD2 and SIX1 ; or at least PLOD2 and JAK1 ; or at least TK2 and SIX1 ; or at least TK2 and JAK1 ; or at least SIX1 and JAK1 ; or at least SIX1 ; PLOD2 and TK2; or at least SIX1 , PLOD2 and JAK1 ; or at least SIX1 , TK2 and JAK1 ; or at least TK2, PLOD2 and JAK1 ; or at least SIX1 , PLOD2; TK2 and JAK1 ; or at least PLOD2, JAK1 and H19; or at least PLOD2, SIX1 and JAK1 ; or at least PLOD2, SIX1 and PCDHA1 ; or at least PLOD2, SIX1 and S100A1 ; or at least PLOD2, JAK1 and MRPS16; or at least PLOD2, SIX1 and TK2; or at least PLOD2, SIX1 and C8orf75; or at least PLOD2, SIX1 and CDH4; or at least PLOD2, SIX1 and LOC100131756; or at least PLOD2, SIX1 and ZC3H12B; or at least PLOD2, SIX1 and CHAC2; or at least PLOD2, JAK1 and EIF2AK2; or at least PLOD2, SIX1 and PCDHB15; or at least PLOD2, SIX1 and VGLL4; or at least PLOD2, RHOU and SIX1 ; or at least PLOD2, SIX1 and APOL6; or at least PLOD2, JAKI and ST8SIA4; or at least PLOD2, SIX1 and CCNO; or at least PLOD2, JAK1 and PCDHB14; or at least PLOD2, SIX1 and ITGA4; or at least PLOD2, JAK1 and PCDHB18; or at least PLOD2, SIX1 and PPIF; or at least PLOD2, SIX1 and TMEM63A; or at least PLOD2, SIX1 and RPS6KL1 ; or at least PLOD2, RHOU and CSPP1 ; or at least PLOD2, SIX1 and FUT6; or at least PLOD2, SIX1 and SIDT2; or at least PLOD2, SIX1 and HAVCR2; or at least PLOD2, SIX1 and C5orf4; or at least PLOD2, SIX1 and CES3; or at least PLOD2, SIX1 and C14orf39; or at least PLOD2, SIX1 and TRD@; or at least PLOD2, SIX1 and TAP2.

The invention further discloses kits that are useful in the above methods. Indeed is provided a kit for predicting responsiveness of a cancer patient to a therapy comprising a treatment with a taxane, said kit comprising means for detecting the panel of markers according to the invention.

They can be used, e.g. for evaluating a cancer patient for propensity to respond to a therapy, and/or for monitoring efficiency of a treatment of cancer, and/or for prognosing or classifying the outcome of cancer. In one embodiment, the kit further comprises a control sample indicative of the amount and/or expression level of said at least one gene of table 1 .

The kits according to the invention may for example comprise, in addition to the means for detecting the amount and/or expression level of said at least one gene, one of (i) to (iii) below:

i. a positive control sample indicative of the amount and/or expression level of said at least one gene in a subject suffering from cancer comprising cancer stem like cells;

ii. a negative control sample indicative of the amount and/or expression level of said at least one gene in a healthy individual;

iii. instructions for the use of said kit in monitoring efficiency of cancer therapy, prognosing or classifying the outcome of cancer in a patient and/or determining a therapeutic regimen suitable for treating a subject suffering from a cancer.

Such a kit may for example comprise (i) and (ii), (i) and (iii), (ii) and (iii), or (i), (ii) and (iii).

Means for detecting the amount and/or expression level of said at least one gene of table 1 are well-known in the art. They include, e.g. reagents allowing the detection of said at least one gene mRNA by real-time quantitative-PCR, such as primers specific for said at least one gene of table 1 . When the kit comprises means for real-time quantitative-PCR said at least one gene mRNA detection, the kit may further comprise a second reagent, labeled with a detectable compound, which binds to said at least one gene mRNA synthesized during the PCR, such as e.g. SYBER GREEN reagents.

Means for detecting the amount and/or expression level of said at least one gene of table 1 may also include antibodies specifically binding to said at least one gene. Such means can be labeled with detectable compound such as fluorophores or radioactive compounds. For example, the probe or the antibody specifically binding to said at least one gene may be labeled with a detectable compound. Alternatively, when the kit comprises an antibody, the kit may further comprise a secondary antibody, labeled with a detectable compound, which binds to an unlabelled antibody specifically binding to said at least one gene of table 1 or proteins coded by said at least one gene.

The means for detecting the amount and/or expression level of said at least one gene may also include reagents such as e.g. reaction, hybridization and/or washing buffers. The means may be present, e.g., in vials or microtiter plates, or be attached to a solid support such as a microarray as can be the case for primers and probes.

In some embodiments, said kit comprises a microfluidic plate, such as a TaqMan®

Low Density Array (TLDA), or a microarray, such as an Affimetrix® microarray or an Agilent® microarray, comprising means for detecting the expression of at least one gene as described above, preferably for simultaneously detecting the expression of the 35 genes PLOD2; H19; SIX1 ; PCDHA1 ; S100A1 ; MRPS16; TK2; C8orf75; CDH4; LOC100131756; ZC3H12B; CHAC2; EIF2AK2; PCDHB15; VGLL4; JAK1 ; APOL6; CCNO; PCDHB14; ITGA4; PCDHB18; PPIF; RHOU; ST8SIA4; TMEM63A; RPS6KL1 ; CSPP1 ; FUT6; SIDT2; HAVCR2; C5orf4; CES3; C14orf39; TRD@ and TAP2.

Preferably, means for detecting the expression of said genes using a TLDA or microarray are oligonucleotides. For example, when using a TLDA, each well of the TLDA according to the invention comprises a forward primer, a reverse primer and a probe, such as a fluorescent probe (e.g. a Taqman probe). For example, when using a microarray, each spot of the microarray comprises a probe, such as a fluorescent probe, specific for each of the said gene. Preferably, said specific probes are Affimetrix probes with the Set Identification Number (Set ID) as described in the Table 1 below.

Although having distinct significances, the terms "comprising", "containing", and "consisting of" were used in an interchangeable way in the description of the invention, and can be replaced one by the other.

Summary of the sequences described herein:

Table 1 :

Table 1 (next)

Probe set I D database: http://genecards.weizmann.ac.il/geneannot/index.shtml BRIEF DESCRIPTION OF THE FIGURES

Fig 1 : Sustained proliferation (KI67) and absence of apoptosis (cleaved caspase 3) after 2 days of culture compared to day 0 (n=25). Apoptosis was assessed in non treated tumors at day 0 (dO) and after 48h (d2) of culture. Shown are the index of proliferation (A) and the index of death (B).

Fig 2 Sustained proliferation (KI67) after 2 days of culture compared to day 0 (n=25) and significant effect of Paclitaxel treatment. Proliferation was assessed in non treated tumors at day 0 (dO), non treated tumors after 48h ((-) d2) of culture and Paclitaxel treated tumors after 48h ((+) d2) of culture; ( ^* ) p<0,05; ( ^*** ) p<0,001 (One-way ANOVA).

Fig 3: Average and standard deviation of apoptosis (cleaved caspase 3) tumor slices taken from different regions within 6 different tumors and treated with a pro apoptotic reagent. The six columns correspond to the 6 different tumors: #47; #55; #64; #70; #72 and #76. Variability in the level of apoptosis seen in different slices taken from the same tumor is very low.

Fig 4: Paclitaxel sensitivity of tumor slices.

EXAMPLES

EXAMPLE 1 : Material and methods

Protocol

Fresh human mammary samples were obtained from patients with invasive carcinoma after surgical resection at the Institut de Cancerologie de I'Ouest - Rene Gauducheau, Nantes, France. Informed consent was obtained from patients to use their surgical specimen and clinicopathological data for research purpose according to the French Committee for the protection of Human Subjects.

A fragment of tumor sample was snapped frozen and stored at -80 °C until transcriptomic analysis.

A second fragment of the same tumor was cut into thin slices (250μηι) using a vibratome (Microme, France) and incubated for 48h in a definite medium with or without 700nM Paclitaxel.

Slices were then fixed in 10% buffered formalin and paraffin embedded. Sections (3μηι) from formalin-fixed, paraffin-embedded tumors were cut for standard histological analysis assessed by hematoxylin-eosin-saffron (HES) coloration. Immunohistochemistry was performed to assess tumoral cell apoptosis with cleaved caspase 3 antibody.

Briefly, after deparaffinisation in xylene and rehydratation, endogenous peroxidase activity was blocked with 3% hydrogen peroxide. Samples were steamed for antigen retrieval with citrate buffer (pH6.0). Slides were incubated for Active Caspase 3 (clone C92-605, dilution 1 :1200) on an automated immunostainer (Autostainer Plus, Dako) using a standard labelled streptavidin-biotin method (Dako, LSAB+, Dako REAL Detection Systems kit) followed by 3,3'- diaminobenzidine chromogen detection. Immunostained slides were counterstained with hematoxylin (Dako). Negative controls (omission of the primary antibody) were included in each run.

The active caspase 3 immunostained cells were assessed according the percentage of labeled cells out 200 carcinomatous cells counted. Non neoplastic cells (endothelial cells and lymphocytes) were excluded from counting.

Validation of the method:

Sustained proliferation and absence of spontaneous apoptosis was assessed in non treated tumors (n=23) at day 0 (dO) and after 48h (d2) of culture (Fig 1 ). Figure 1 shows a comparison of the index of proliferation (FigI A) and death (FigI B).

Proliferation status, assessed by KI67 staining, was analyzed at day 0 (immediately after surgery) and at day 2 (after 2 days of culture). At day 0, the mean of proliferating tumoral cells is 39,61 % (±4,85 SEM) whereas it is 28,63% (±4,09 SEM) at day 2 (FigI A). There is therefore a slight decrease in the overall proliferation of cells during ex vivo culture. The decrease in proliferation is, moreover, much less important than that observed between an untreated slice of tumor and a slice of the same tumor treated with paclitaxel (Fig 2).

Spontaneous apoptosis rates (percentage of active casp3 + tumor cells) at day 0 are comprised between 0 and 14% (mean 2,091 ±0,67 SEM) whereas apoptotic rates at day 2 are comprised between 0 and 12,5 (mean 6,043±0,75 SEM) (Fig1 B). Despite a very slight increase in apoptosis after 2 days, this is never above the maximal value observed for dO (i.e 14%). From Figure 1 , we can conclude that not only do the cells not die with this technique, but they maintain an almost normal proliferative capacity, suggesting a continuation of metabolism and proliferative signals. In contrast, paclitaxel induces a strong cell cycle arrest and apoptosis.

Apoptosis was also assayed in duplicate and triplicate tumor slices taken from 6 different tumors. The six columns correspond to the 6 different tumors. Slices were taken from different locations (from 1 ,5mm to 2mm of the previous slice) within the tumor and treated with the same reagent. As can be seen from Figure 3, the level of apoptosis seen in different slices taken from the same tumor is very slight: the standard error is comprised between 0,5 and 9 (mean 4,54±1 ,71 SEM). This indicates that tumor response, in the ex vivo assay to a given treatment is independent of the localization of the tissue slice within the tumor sample, demonstrating the reproducibility of the method.

Paclitaxel sensitivity:

After this validation step, the response of tumor slices to 700nM Paclitaxel treatment was assessed. 16 different tumors were analysed. Tumor slices were either treated with paclitaxel for 48h or left untreated (control). After culture, slices were fixed and assessed for apoptosis as previously described. Tumors were then classified as "sensitive" or "resistant" according to their response to treatment (Fig 4). The apoptotic rates of non treated slices were 5,22% (±0,97 SEM). For calculation facility we considered it at 5,5%. Slices were classified as sensitive if their measured apoptotic rates were 4 times greater than that found in the non treatedgroup, ie above 22% of apotosis. We thus obtained 2 groups of tumors: the resistant one with a mean response of 12,3% (±2,48 SEM) and the sensitive one with a mean response of 29,6% (±1 ,18 SEM). The difference between the 2 groups was significative (p<0,001 ) whereas the difference between the untreated and the resistant groupswas not (p=0,06).

There are no differences in the apoptotic rates at day 2 in the absence of treatment between the resistant and sensitive groups (5,71 ±1 ,76 SEM vs 7,67±1 ,07 SEM, p=0,43) . The proliferation rates are also similar (26,44±7,72 SEM vs 35,4±10,68 SEM, p=0,5). Furthermore, there is no difference in KI67 staining between the resistant and sensitive group after paclitaxel treatment (14,64±8,1 SEM vs 24,9±1 1 ,63 SEM, p=0,46). This indicates that cell cycle blocking is efficient in both cases (confirming that paclitaxel has an effect) and that other mechanisms are involved in inducing cell death. These mechanisms have been investigated by affymetrix analysis.

Tumor fragments from tumor bank were then used for affymetrix analysis.

Affymetrix analysis

RNA preparation.

Total RNAwas extractedfor macrodissected tumors using TRIzol® (Invitrogen) and cleaned up from the lysate using the MinElute Reaction Cleanup Kit (Qiagen).RNA purity and integrity werecontrolled by an Agilent 2100 Bioanalyser(Agilent Technologies). DNA microarray analysis.

Samples were prepared according to the manufacturer'sinstructions. Experiments to generate gene-expression signature used GeneChip® Human Genome U133 Plus 2.0 Array and 3' IVT express Kit (Affymetrix, Santa Clara, CA, USA). Statistical analysis

Genes differentially expressed among taxol response were determined by means of permutation techniques using BRB-ArrayTools v4.2.0 developed by Dr. Richard Simon and BRB-ArrayTools Development Team.

Results obtained are presented in table 2. Data were analyzed according to the BRB-Array tools (http://linus.nci.nih.gov/BRB-ArrayTools.html) as described in the prior art (Korde LA. et al, Breast Cancer Res Treat. 2010 Feb;1 19(3):685-99; Rabinovich El et al., PLoS One. 2012;7(4):e33770. Epub 2012 Apr 10). Briefly, the data shown is generated by the comparison of gene expression values between responders (R) and nonresponders (S). The columns "Geometric mean of R or S Intensities in patients" quantify the expression in responders and non-responders respectively, which were used to calculate "fold-change" (calculated as Intensity R / Intensity S). The column "Parametric p-value" quantifies the likelihood of a parametric difference between R and S (Wilcoxon test standard). The columns "FDR" and "Permutation p-value" quantify the same probability taking into account the risk of false positives inherent to the large number of comparisons made, confirming the interest of a gene if the FDR and permutation p-value are small (close to 0001 or smaller than 0001 ). In table 2, the letter "X" refers to unidentified genes.

Most of the genes of table 2 can be classified within different groups: i extracellular matrix adhesion (PCDH family, PLOD2, ITGA4, FUT6), ii epithelio-mesenchymal transition/migration (SIX1 , RHOU, ST8SIA4, CDH4) iii chemotherapy resistance (TK2, CES3, TAP2). These different pathways could be involved in tumor cell fate after paclitaxel treatment, being able to regulate survival. The absence of genes involved in cell cycle correlates with the previous observation that no difference could be observed between the proliferation status of the 2 groups. Table 2

Gene Taxol Parametric FDR Permutation Geom Geom Fold symbol 0.001 p-value p-value mean of mean of change

1Nv2 intensities intensities

ordre in R in S

patients patients

PLOD2 1 0,0000677 0,00995 0,0003 140,7 382,36 0,37 Up in S

H19 2 7,41 E-05 0,00995 3,00E-04 1434,7 54,01 26,56 Up in R

X 3 0,0001445 0,00995 0,001 33,14 5,89 5,63 Up in R

SIX1 4 0,0001513 0,00995 0,001 106,45 3 35,43 Up in R

PCDHA 5 0,0001755 0,00995 0,0013 309,57 53,78 5,76 Up in R 1

S100A1 6 0,0002945 0,00995 0,0016 303,6 19,43 15,62 Up in R

MRPS1 7 0,0002951 0,00995 3,00E-04 245,56 384,12 0,64 Up in S 6

TK2 8 0,0003086 0,00995 8,00E-04 81 ,4 46,24 1 ,76 Up in R

C8orf75 9 0,0003141 0,00995 5,00E-04 5,8 10,14 0,57 Up in S

CDH4 10 0,0003159 0,00995 7,00E-04 9,49 16,94 0,56 Up in S

X 1 1 0,0003566 0,00995 0,0012 100,13 214,08 0,47 Up in S

LOC10 12 0,0003667 0,00995 0,001 1 3,57 9,85 0,36 Up in S 013175

6

X 13 0,000424 0,00995 0,0017 8,42 3,68 2,29 Up in R

ZC3H1 14 0,000431 0,00995 9,00E-04 6,48 1 1 ,73 0,55 Up in S 2B

PCDHA 15 0,0004364 0,00995 0,0024 143,34 15,69 9,13 Up in R 1

CHAC2 16 0,0004483 0,00995 8,00E-04 57,96 182,97 0,32 Up in S

EIF2AK 17 0,0004536 0,00995 9,00E-04 12,78 39,24 0,33 Up in S 2

PCDHB 18 0,0005179 0,00995 0,0013 29,25 1 1 ,9 2,46 Up in R 15

VGLL4 19 0,0005405 0,00995 0,0013 1067,95 353,53 3,02 Up in R

JAK1 20 0,0005515 0,00995 0,0013 33,92 80,89 0,42 Up in S

APOL6 21 0,0005647 0,00995 0,0019 95,27 318,04 0,3 Up in S

ST8SIA 22 0,0005833 0,00995 0,0019 35,06 94,44 0,37 Up in S 4

CCNO 23 0,0006124 0,00995 0,0019 192,51 14,45 13,32 Up in R

X 24 0,0006359 0,00995 0,0017 81 ,69 1 1 ,62 7,03 Up in R

PCDHA 25 0,0006517 0,00995 0,0019 270,91 37,57 7,21 Up in R 1 Table 2 (next)

overexpressed in patients sensi ive to paclitaxel

Up in R: overexpressed in patients resistant to paclitaxel