Implementation of BRCA mutations testing in formalin-fixed paraffin-embedded (FFPE) samples of different cancer types

Abstract

BRCA1 and BRCA2 are onco-suppressor genes involved in the DNA repair mechanism. The presence of BRCA1/2 mutations confers a higher risk of developing several cancer types. To date, the FDA approved various PARP inhibitors to treat selected BRCA1/2 mutated oncologic patients. At first, PARP inhibitors were approved for patients with ovarian and breast cancers, and subsequently for metastatic pancreatic adenocarcinoma and metastatic castration-resistant prostate cancer after the treatment with chemotherapy. The current guidelines for BRCA testing are very heterogeneous between the different types of tumors regarding the diagnostic algorithm and the type of sample to analyze, such as the blood for the germline mutations and the tumoral tissue for the somatic mutations. Few data have currently been described regarding the detection of BRCA1/2 somatic mutations in formalin-fixed paraffin-embedded (FFPE) samples. In this review, we propose an overview of the BRCA mutations in FFPE samples of several cancers, including breast, ovarian, fallopian tube, primary peritoneal, prostate, and pancreatic cancer. We summarize the types and the frequency of BRCA mutations, the guidelines approved for the test, the molecular assays used for the detection and the PARP inhibitors approved for each tumor type.

Keywords: Formalin-fixed paraffin-embedded; Next generation sequencing; PARP inhibitors; Somatic BRCA mutations.