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Cancer Biol Ther. 2010 Sep 15;10(6):582-7. Epub 2010 Oct 1.

Prioritization of driver mutations in pancreatic cancer using cancer-specific high-throughput annotation of somatic mutations (CHASM).

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Department of Biomedical Engineering and Institute for Computational Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.


Over 20,000 genes were recently sequenced in a series of 24 pancreatic cancers. We applied CHASM (Cancer-specific High-throughput Annotation of Somatic Mutations) to 963 of the missense somatic missense mutations discovered in these 24 cancers. CHASM identified putative driver mutations (false discovery rate ≤0.3) in three known pancreatic cancer driver genes (P53, SMAD4, CDKN2A). An additional 15 genes with putative driver mutations include genes coding for kinases (PIK3CG, DGKA, STK33, TTK and PRKCG), for cell cycle related proteins (NEK8), and for proteins involved in cell adhesion (CMAS, PCDHB2). These and other mutations identified by CHASM point to potential "driver genes" in pancreatic cancer that should be prioritized for additional follow-up.

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