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. 2022 Mar 10;14(6):1434.
doi: 10.3390/cancers14061434.

Real-World Data on Detection of Germline and Somatic Pathogenic/Likely Pathogenic Variants in BRCA1/2 and Other Susceptibility Genes in Ovarian Cancer Patients Using Next Generation Sequencing

Vida Stegel  1 , Ana Blatnik  2 , Erik Škof  3 , Vita Šetrajčič Dragoš  1 , Mateja Krajc  2 , Brigita Gregorič  3 , Petra Škerl  1 , Ksenija Strojnik  2 , Gašper Klančar  1 , Marta Banjac  2 , Janez Žgajnar  4 , Maja Ravnik  5 , Srdjan Novaković  1
Affiliations

Real-World Data on Detection of Germline and Somatic Pathogenic/Likely Pathogenic Variants in BRCA1/2 and Other Susceptibility Genes in Ovarian Cancer Patients Using Next Generation Sequencing

Vida Stegel et al. Cancers (Basel). .

Abstract

Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.

Keywords: BRCA; HBOC; PARP inhibitors; germline genotyping; ovarian cancer; reverse mutation; tumor genotyping.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Scheme 1
Scheme 1
Study workflow.
Scheme 2
Scheme 2
Comparison of testing scenarios—germline genotyping first vs. tumor genotyping first.
See this image and copyright information in PMC

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