Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in <i>BRCA1/2</i>: results of the observational AGO-TR1 study (NCT02222883).

ABSTRACT: Variant-specific loss of heterozygosity (LOH) analyses may be useful to classify BRCA1/2 germline variants of unknown significance (VUS). The sensitivity and specificity of this approach, however, remains unknown. We performed comparative next-generation sequencing analyses of the BRCA1/2 genes using blood-derived and tumour-derived DNA of 488 patients with ovarian cancer enrolled in the observational AGO-TR1 trial (NCT02222883). Overall, 94 pathogenic, 90 benign and 24 VUS were identified in the germline. A significantly increased variant fraction (VF) of a germline variant in the tumour indicates loss of the wild-type allele; a decreased VF indicates loss of the variant allele. We demonstrate that significantly increased VFs predict pathogenicity with high sensitivity (0.84

SUBMITTER: Hauke J 

PROVIDER: S-EPMC8867275 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature