Missense variants in Lynch Syndrome genes in endometrial cancer patients characterized by The Cancer Genome Atlas (TCGA) project.

Abstract

1547 Background: We sought to characterize the missense variants in the Lynch Syndrome genes in patients with endometrial cancer that had normal germline DNA characterized by TCGA. Methods: We obtained institutional IRB approval and approval from the National Center for Biotechnology Information Genotypes and Phenotypes Database (NCBI dbGaP) for data access to TCGA data files. We utilized Variant Call Format (VCF) files to annotate germline single nucleotide variants in exomic regions of the Lynch Syndrome genes (MLH1, MSH2, MSH6, PMS2) among 248 patients with endometrial cancer. We used the MetaLR composite score from Annovar, which combines data from SIFT, PolyPhen2, LRT, MutationTaster, MutationAssessor, FATHMM, GERP++, PhyloP and SiPhy for prediction of variant effects on protein function. Results: A total of 120 different missense variants from 248 patients were found in the Lynch Syndrome genes (8 in MLH1, 26 in MSH2, 41 in MSH6, 45 in PMS2). 82 (68%) of these variants were novel and were not annota...