Abstract IA07: Germline next-generation sequencing panels for detection of inherited colorectal cancer syndromes

Abstract

Abstract Background: Germline genetic testing for hereditary cancer predisposition syndromes can prevent cancer and save lives by identifying individuals who will benefit from enhanced surveillance, prophylactic surgery, and other risk-reduction strategies. Classically, hereditary cancer risk assessment has involved identification of individuals with clinical histories that fulfill specific criteria for a given syndrome followed by germline testing for mutations in the associated gene(s). Recent advances in next-generation sequencing technologies now allow individuals to undergo germline evaluation of numerous genes in parallel and a growing array of multigene panels are clinically available for such diagnostic testing. Methods: This presentation will discuss updates in clinical genetic testing, specifically the growing availability of next-generation sequencing multigene panel testing for hereditary cancer risk assessment. Findings: Data regarding next-generation sequencing multigene panel testing will be presented and will be contrasted with traditional, syndrome-specific hereditary colorectal cancer risk assessment strategies. Particular areas of focus in this talk will include: the detection of unexpected/off-target germline mutations by multigene panels (e.g. BRCA1/2 mutations in patients with colorectal cancer); cost-effectiveness considerations; the significance of moderate-penetrance cancer susceptibility gene mutations; germline variants of uncertain significance; and ways in which multigene panel testing results are expanding knowledge (and uncertainty) about both well- and poorly-defined colorectal cancer predisposition syndromes. Conclusions: Next-generation sequencing multigene panels are rapidly growing in popularity and availability for assessing hereditary cancer risk, including the identification of germline mutations linked to inherited colorectal cancer risk. In order for patients considering such testing to receive optimal care, it is essential that both they and their providers have a clear understanding of the benefits and potential limitations of multigene panels, including the possibility of identifying unexpected and/or indeterminate germline results. Citation Format: Matthew B. Yurgelun. Germline next-generation sequencing panels for detection of inherited colorectal cancer syndromes. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA07.