Detection of BRCA1/2 large genomic rearrangements in breast and ovarian cancer patients: an overview of the current methods

Introduction: Currently, genetic testing of BRCA1/2 genes includes screening for single-nucleotide variants, small insertions/deletions, and copy number variations (CNVs). In fact, many studies document the involvement of BRCA1/2 gene rearrangements in genetic predisposition to breast and ovarian cancer. Large genomic rearrangements (LGRs) of BRCA1 may account for up to one-third of all disease-causing alterations in various populations, while LGRs in BRCA2 are less frequently observed. Areas covered: We aimed to present an overview of current technologies employed in molecular diagnosis of BRCA1/2 LGRs. The most relevant literature papers, showing the application of new strategies, were considered. Expert opinion: Currently, the progress of next-generation sequencing (NGS) technologies allows for the validation of new pipelines able to provide rapid and effective results, ensuring the sensitivity and specificity requested for the detection of BRCA1/2 LGRs. Multiplex ligation-dependent probe amplification remains the gold standard to confirm NGS CNVs results and to perform fast screening in families where a pathogenic rearrangement has been detected in a proband.