Functional analysis of clinical BARD1 germline variants.

ABSTRACT: Germline pathogenic variants in BRCA1/2 account for one-third of familial breast cancers. The majority of BRCA1 function requires heterodimerization with BARD1. In contrast to BRCA1, BARD1 is a low-penetrance gene with an unclear clinical relevance, partly because of limited functional evidence. Using patient-derived lymphoblastoid cells, we functionally characterized two pathogenic variants (c.1833dupT, c.2099delG) and three variants of uncertain significance (VUSs) (c.73G>C, c.1217G>A, c.1918C>A). Three of these patients had breast cancers, whereas the remaining had colorectal cancers (n = 3). Both patients with pathogenic variants (c.1833dupT, c.2099delG) developed breast cancers with aggressive disease phenotypes such as triple-negative breast

SUBMITTER: Toh MR 

PROVIDER: S-EPMC6672023 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature