Impact of germline and somatic BRCA1/2 mutations: tumor spectrum and detection platforms

The BRCA1/2 genes are long and complex and mutation carriers are at risk of developing malignancies, mainly of gynecological origin. Various mutations arise in these genes and their characterization is a time-consuming, cost intensive, complicated process. Tumors of BRCA1/2 origin have distinct molecular and histological features that can impact responses to therapy. Therefore, detection of these mutations constitutes an important step in the risk assessment, prevention strategy and treatment of subjects. Although Sanger sequencing is the gold standard for the detection of genetic mutations, several next generation sequencing-based high throughput platforms have been developed and adapted for the detection of BRCA1/2 mutations. This review provides a comprehensive overview of the sequencing platforms available for the screening and identification of these mutations. We also summarize what is known about the different types of mutations that arise in these genes and the tumor spectra they result in. Finally, we present a short discussion on existing clinical guidelines which assist physicians in the decision-making process. These parameters have important consequences for the management of patients and an urgent need exists for the development of detection platforms that are cost effective and can provide clinicians with conclusive results within a significantly shorter time.