A Multi-Gene Mutation Classification of 468 Colorectal Cancers Reveals a Prognostic Role for APC

Study ID Alternative Stable ID Type
phs001111 Case Set

Study Description

Colorectal cancer (CRC) is a highly heterogeneous disease, for which prognosis has been relegated to clinic-pathologic staging for decades. There is a need to molecularly stratify subpopulations of CRC to better predict outcome and assign therapies. Here we report targeted exome sequencing of 1,321 cancer-related genes on 468 tumor specimens, which identified a subset of 17 genes that best classify CRC, with APC (Gene ID: 324) playing a central role in predicting overall survival. APC may assume 0, 1, or 2 truncating mutations, each with a striking differential impact on survival. Tumors lacking any APC mutation carry a worse prognosis than single APC mutation tumors, but tumors with two APC mutations and KRAS (Gene ID: 3845) and TP53 (Gene ID: 7157) mutations confer the poorest survival among all the subgroups examined. Our study demonstrates a substantial prognostic role for APC and suggests that sequencing of APC may have clinical utility in the routine staging and potential therapeutic assignment for CRC.

Archive Link Archive Accession
dbGaP phs001111

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