Abstract 3372: Mutations of mismatch repair genes in Her2 overexpressed breast cancer

Abstract

Abstract The importance of Mismatch Repair (MMR) in therapeutic selection is an area of recent research. Minority of unselected breast tumors exhibit mutations indicative of deficient MMR. Here, we present our preliminary data investigating 7 MMR genes exclusively in Her2-overexpressed (Her2OE) breast cancer (BC). Twenty-five archival formalin-fixed paraffin-embedded samples from 25 Her2OE BC patients underwent targeted next generation sequencing for 7 MMR genes (MLH1, MLH3, MSH2, MSH6, PMS2, POLD1 and EPCAM). The analysis was performed through the Saudi Human Genome Project bioinformatics pipeline. Data filtration was performed to rank genetic variants based on their predicted pathogenicity. Methods of filtration included mutation effect, ClinVar findings, ExAC loss of function index (pLI) and collective proteomics index. Twenty-four out of 25 (96%) tumors contained significant mutations in one or more MMR genes. Three cases (12%) contained mutations in 3-4 MMR genes while 21 (84%) had 1-2 alteration(s) in these gene(s). Only one case showed no significant mutations in any of the studied MMR genes. MLH1, MLH3, MSH2, MSH6, PMS2, POLD1 and EPCAM were mutated in 6(24%), 1(4%), 5(20%), 18(72%), 2(8%), 6(24%) and 3(12%) respectively. In this preliminary report, mutations in MMR genes affect up to 96% of Her2OE BC tumors. Such result may impact on therapeutic choices. This result is to be confirmed in larger cohort. Citation Format: Mohammed A. Baghdadi, Turki M. Sobahy, Hosam A. Alardati, Jamal E. Zekri. Mutations of mismatch repair genes in Her2 overexpressed breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3372.