Exploring alternatives to tumor tissue for <i>BRCA1/2</i> next‐generation sequencing testing in high‐grade serous ovarian cancer: A 34‐case series of malignant ascites

BACKGROUND: BRCA1/2 testing is currently recommended at diagnosis for high-grade serous ovarian carcinoma (HGSOC) because of its impact on patients' survival when treated with poly(adenosine diphosphate ribose) polymerase inhibitors. Standard clinical practice involves analyzing BRCA1/2 genes in formalin-fixed, paraffin-embedded (FFPE) histological specimens. However, because neoplastic ascites is a common clinical presentation in HGSOC and provides a good source of neoplastic cells via a less invasive procedure, it is worthwhile to explore the feasibility of BRCA1/2 testing on cytological specimens obtained from malignant ascites. METHODS: BRCA1/2 status was analyzed in 34 ascites-derived cytological samples via an amplicon-based next-generation sequencing (NGS) approach, and the results were compared with those from FFPE tissues previously tested in routine clinical practice. RESULTS: A perfect match was observed between BRCA1/2 testing results from neoplastic ascites and surgical samples (100% concordance) for all pathogenic variants, including both germline and somatic mutations. This is the first study to report such high concordance within the largest collection of somatic variants analyzed to date. Additionally, molecular NGS testing was demonstrated to be feasible even in malignant ascites with a low tumor fraction and with archived material. CONCLUSIONS: This study shows that ascites can be a suitable specimen for BRCA1/2 NGS testing, and provides a minimally invasive option for disease diagnosis and the early detection of key molecular biomarkers essential for the clinical management of women with HGSOC.