Unexpected Findings in Hereditary Breast and Ovarian Cancer Syndrome: Low-Level Constitutional Mosaicism in <i>BRCA2</i>

Abstract

Hereditary breast and ovarian cancer syndrome (HBOC) is a clinical entity characterized by an increased risk of developing breast and ovarian cancer. The genetic diagnosis is based on the identification of heterozygous germinal variants in HBOC susceptibility genes. However, it has recently been described that constitutional mosaic variants can contribute to the aetiology of HBOC. In constitutional mosaicism, individuals have at least two genotypically distinct populations of cells that arise from an early post-zygote event. The mutational event occurs early enough in development to affect several tissues. It is detected in germinal genetic studies as low variant allele frequency (VAF) variants (A mosaic variant in the BRCA2 gene and propose a diagnostic algorithm to deal with potential mosaic findings identified by Next Generation Sequencing (NGS).

Keywords

• HBOC
• constitutional mosaicism
• <i>BRCA2</i>