20Oct 2023
Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non‐high‐grade serous ovarian carcinomas

Causality and functional relevance of BRCA1 and BRCA2 pathogenic variants in non‐high‐grade serous ovarian carcinomas

The study analyzed BRCA1/2 tumor sequencing in a prospective series of 946 epithelial ovarian carcinomas (EOCs) of different histotypes. It revealed that BRCA1/2 pathogenic variants (PVs) were present in 125 samples (13%), primarily concentrated in high-grade serous ovarian carcinomas (HGSOC). Interestingly, these variants were also found in specific non-HGSOC histotypes, including high-grade endometrioid, low-grade endometrioid, low-grade serous, and clear cell EOCs, but were notably absent in mucinous ovarian carcinomas. Further analysis identified potentially misclassified cases and variants likely causal in carcinogenesis, suggesting the need for histotype-directed sequencing. The study emphasizes the importance of in-depth functional analysis and histotype revision for a better understanding of BRCA1/2-related cancers.

  • #oncology

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