MUTANT PROTEINS AS CANCER-SPECIFIC BIOMARKERS

WIPO Patent Application WO/2012/099881

A3

Altered protein products resulting from somatic mutations are directly identified and quantified by mass spectrometry. The peptides expressed from normal and mutant alleles are detected by Selected Reaction Monitoring (SRM) of their product ions using a triple quadrupole mass spectrometer. As a prototypical example of this approach, we quantify the number and fraction of mutant Ras protein present in cancer cell lines. There were an average of 1.3 million molecules of Ras protein per cell and the ratio of mutant to normal Ras proteins ranged from 0.49 to 5.6. Similarly, we detected and quantified mutant Ras proteins in clinical specimens such as colorectal and pancreatic tumor tissues as well as in pre-malignant pancreatic cyst fluids. These methods are useful for diagnostic applications.

VOGELSTEIN BERT (US)
WANG QING (US)
PANDEY AKHILESH (US)
KINZLER KENNETH W (US)
PAPADOPOULOS NICKOLAS (US)

PCT/US2012/021553

October 26, 2012

January 17, 2012

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UNIV JOHNS HOPKINS (US)
VOGELSTEIN BERT (US)
WANG QING (US)
PANDEY AKHILESH (US)
KINZLER KENNETH W (US)
PAPADOPOULOS NICKOLAS (US)

G01N33/68; G01N33/551; G01N33/574

US20100086960A1	2010-04-08
US20100105101A1	2010-04-29
US20100297667A1	2010-11-25

LENNY, D. ET AL.: "Cancer-associated IDH1 mutations produce 2-hydroxyglutara te", NATURE., vol. 462, no. ISSUE, December 2009 (2009-12-01), pages 739 - 744, XP055009217, DOI: doi:10.1038/nature08617
WANG, Q. ET AL.: "Mutant proteins as cancer-specific biomarkers", PNAS, vol. 108, no. ISSUE, 8 February 2011 (2011-02-08), pages 2444 - 2449

KAGAN, Sarah A. (1100 13th Street, N.W.,Suite 120, Washington District of Columbia, US)

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