Abstract P5-03-04: Co-segregation of rare possibly-damaging variants in cancer-related genes correlates with phenotypic homogeneity in familial breast cancer

BACKGROUND Breast cancer (BC) is a complex disease. While Mendelian mutations in high-penetrance genes predispose to some familial forms, others are due to multiple common low-penetrance polymorphisms. However, it is unclear if the combination of some rare coding variants has an effect. As some Mendelian forms demonstrate genotype-phenotype correlations, we hypothesized co-segregation of rare variants in cancer-related genes would be more frequent in high-risk families with a uniform BC phenotype among relatives. METHODS Whole-exome sequencing was performed on germline DNA from unrelated BC patients referred for genetic testing but without a causative mutation and for which DNA was available from at least one second relative with BC. We retained rare ( Citation Format: Cedric Van Marcke, Raphael Helaers, Celine A Schoonjans, Jerome Ambroise, Martine Berliere, Jean-Luc Canon, Peter Vuylsteke, Jean-Pascal Machiels, Miikka Vikkula, Francois P Duhoux. Co-segregation of rare possibly-damaging variants in cancer-related genes correlates with phenotypic homogeneity in familial breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-04.