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. 2021 Nov 28;12(12):1917.
doi: 10.3390/genes12121917.

BRCA1/2 NGS Somatic Testing in Clinical Practice: A Short Report

Francesco Pepe  1 , Pasquale Pisapia  1 , Gianluca Russo  1 , Mariantonia Nacchio  1 , Pierlorenzo Pallante  2 , Elena Vigliar  1 , Carmine De Angelis  3 , Luigi Insabato  4 , Claudio Bellevicine  1 , Sabino De Placido  3 , Giancarlo Troncone  1 , Umberto Malapelle  1
Affiliations

BRCA1/2 NGS Somatic Testing in Clinical Practice: A Short Report

Francesco Pepe et al. Genes (Basel). .

Abstract

High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of all ovarian carcinomas. HGSOC harboring BRCA1/2 germline or somatic mutations are sensitive to the poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi). Therefore, detecting these mutations is crucial to identifying patients for PARPi-targeted treatment. In the clinical setting, next generation sequencing (NGS) has proven to be a reliable diagnostic approach BRCA1/2 molecular evaluation. Here, we review the results of our BRCA1/2 NGS analysis obtained in a year and a half of diagnostic routine practice. BRCA1/2 molecular NGS records of HGSOC patients were retrieved from our institutional archive covering the period from January 2020 to September 2021. NGS analysis was performed on the Ion S5™ System (Thermo Fisher Scientific, Waltham, MA, USA) with the Oncomine™ BRCA Research Assay panel (Thermo Fisher Scientific). Variants were classified as pathogenic or likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics by using the inspection of Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) and ClinVar (NCBI) databases. Sixty-five HGSOC patient samples were successfully analyzed. Overall, 11 (16.9%) out of 65 cases harbored a pathogenic alteration in BRCA1/2, in particular, six BRCA1 and five BRCA2 pathogenic variations. This study confirms the efficiency and high sensitivity of NGS analysis in detecting BRCA1/2 germline or somatic variations in patients with HGSOC.

Keywords: BRCA1/2; HGSOC; NGS; PARPi; molecular pathology.

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Conflict of interest statement

Umberto Malapelle has received personal fees (as consultant and/or speaker bureau) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientifics, Eli Lilly, Diaceutics, GSK, Merck and AstraZeneca, unrelated to the current work. Giancarlo Troncone reports personal fees (as speaker bureau or advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen and Bayer, unrelated to the current work. Carmine De Angelis has received personal fees (as consultant and/or speaker bureau) from Roche, Eli Lilly, GSK, Novartis, Pfizer and AstraZeneca, unrelated to the current work. Sabino De Placido has received personal fees (as consultant and/or speaker bureau) from Novartis, Roche, Celgene, AstraZeneca, Pfizer, Lilly, Eisai, Seagen, Daiichi Sankyo, Clovis, GSK, MSD, unrelated to the current work. The other authors have nothing to disclose.

Figures

Figure 1
Figure 1
BRCA1/2 molecular evaluation with NGS approach: an exemplificative case. This Figure also shows a neoplastic area for DNA extraction (A), loading density (B), and technical quality parameters (C) of a NGS run on an Ion Torrent S5 ™ platform (Thermo Fisher Scientifics). Box (D) shows a BRCA1 p.C61G point mutation with an integrated genetics viewer.
See this image and copyright information in PMC

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