Abstract 3388: Tumor suppressor genes may promote tumorigenesis through allele specific expression

Abstract

Abstract Cancer has long thought to be a disease which develops from de novo cancer driver mutations in oncogenes and tumor suppressor genes (TSGs). The purpose of our study is to examine how TSGs contribute to tumorigenesis. Accordingly, we studied loss-of-function (LoF) mutations in TSGs within 2504 individuals from 1000 Genomes Project (1KGP) and 233 patients across four different cancer types from The Cancer Genome Atlas (TCGA). We found a large fraction of 1KGP individuals were carriers of heterozygous LoF mutations in TSGs. However, compound heterozygosity of LoF mutations in at least one TSG was only found in 20% of our TCGA patients. Further, analysis of allele specific expression (ASE) in these tumors identified several TSGs where the mutant allele is overexpressed relative to the reference allele. This evidence of ASE suggests TSGs have the potential to drive tumorigenesis in the heterozygous condition, if the reference allele is sufficiently repressed. Citation Format: Evan Clayton. Tumor suppressor genes may promote tumorigenesis through allele specific expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3388.