Low-level constitutional mosaicism of a de novoBRCA1 gene mutation

Heterozygous germline mutations in the BRCA1 and BRCA2 (MIM *113705*600185) genes detected in a subset of high-risk breast/ovarian families are used clinically to objectively assess lifetime risks for developing these and other cancer types, and can have an impact on recommendations for early detection and risk-reducing surgeries (Petrucelli et al, 2010). DNA sequencing of the tumour tissue can be used to detect somatic mutations that may define therapeutic targets and refine treatment options (Ross et al, 2013; Ali et al, 2014). However, a third case is rarely considered – somatic mutations in either gene acquired early in embryonic development, which establish a predisposition for disease but which are not detected by traditional sequencing technologies. The gold standard for detecting BRCA genes' sequence variants has long been Sanger sequencing, but recently next-generation sequencing (NGS) technologies have emerged as a highly accurate and efficient alternative (Feliubadalo et al, 2013; Kurian et al, 2014), with improved sensitivity for detection of mosaic events. Here we describe the occurrence of very low-level constitutional mosaicism of a pathogenic BRCA1 gene mutation and the possible implications of this novel finding.