Background: Since the approval of the first poly (adenosine diphosphate [ADP]) ribose polymerase inhibitor (PARPi; olaparib [Lynparza™]) for platinum-sensitive relapsed high grade ovarian cancer, with either germline or somatic BRCA1/2 deleterious variants, the strategies for BRCA1/2 are dynamically changing. Along with germline testing within the context of familial or sporadic ovarian cancer, patients are now being referred for BRCA1/2 genetic assay above all for treatment decisions: in this setting tumour BRCA assay can allow to identify an estimated 3-9% of patients with peculiar somatic BRCA1/2 mutations. These women could also benefit from PARPi therapy. This new type of approach is really challenging, in particular due to the technical and analytical difficulties regarding low quality DNA deriving from formalin-fixed, paraffin-embedded (FFPE) specimens.
Aim: in this manuscript, we try to a) underline many issues related to BRCA1/2 analysis by next generation sequencing technologies (NGS), b) provide some responses to many questions regarding this new paradigm related to OvCa patients' management. Some considerations for incorporating genetic analysis of ovarian tumour samples into the patient pathway and ethical requirements are also provided.
Methods: we used our retrospective data based on thousands of ovarian cancer women sequenced for BRCA1/2 genes.
Discussion: tumor BRCA1/2 assay should be rapidly introduced in routine laboratory practice as first line testing by using harmonized pipelines based on consensus guidelines.
Keywords: NGS; OvCa; molecular diagnostics; tBRCA1/2.