PIK3CA mutations in colorectal and endometrial cancer with double somatic mismatch repair mutations compared to Lynch syndrome.

3550 Background: Double somatic mutations in mismatch repair (MMR) genes have recently been described in a high proportion of colorectal and endometrial cancers with microsatellite instability (MSI) not attributable to MLH1 hypermethylation or germline mutation. We sought to define the molecular phenotype of this new tumor subtype. Methods: We identified patients with double somatic colorectal and endometrial tumors from two Ohio-based prospective Lynch syndrome screening studies who had abnormal tumor testing (MSI and/or by immunohistochemistry (IHC) without coexistent MLH1 methylation), but normal germline MMR testing. We determined the frequency of PIK3CA, BRAF, KRAS, NRAS, and PTEN mutations in double somatic tumors by targeted next-generation sequencing and compared the mutation frequencies to tumors of other MSI sub-groups: Lynch syndrome, MLH1 hypermethylation, and microsatellite stable (MSS) tumors. The frequencies were compared among groups with a logistic regression model. Results: We found that...