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Homologous recombination deficiency in unselected cases of high-grade ovarian carcinoma

jmedgenet · 2025-10-20 · canonical JSON source

2 visible annotations · policy: published · automated confidence ≥ 75.00%

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Germline homologous recombination repair (HRR) gene and tumour homologous recombination deficiency (HRD) testing are standard for women diagnosed with high-grade ovarian carcinoma (HGOC). The biomarker used to determine tumour HRD status is genomic instability (GI). The link between pathogenic variants (PVs) in HRR genes and tumour GI is unknown. We investigated this link in over 1000 cases of HGOC tested by the North West Genomic Laboratory Hub (Manchester, England). We found that over 95% of tumours with a BRCA1 PV had High GI, while only 80% of tumours with a BRCA2 PV and 50% with a PV in a non-BRCA HRR gene had High GI. These data suggest that some HGOCs in high to moderate-risk germline heterozygotes are not germline driven and/or that clinical-grade HRD assays do not detect all true HRD tumours.