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

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.

Evaluation of the Available Variant Calling Tools for Oxford Nanopore Sequencing in Breast Cancer

“…As a result, current worldwide guidelines strongly advise BRCA1/2 testing in all patients. Rapid and dependable genetic screening for BRCA1/2 germline or somatic mutations has become critical in identifying individuals who would most likely benefit from these treatments [ 3 , 33 , 34 ].…”

“…Next-generation sequencing (NGS) is a game-changing high-throughput nucleotide sequencing approach that produces rapid, cheap, and accurate genomic data. NGS developed the clinical methodology for genetic examination across various fields of medicine [ 34 ]. NGS can massively sequence millions of DNA reads, allowing for accurate characterization of the “status” of multiple genes; in this context, NGS-targeted gene sequencing enables the detection of driver mutations, which are responsible for progression and relapse and might be employed as predictive or prognostic biomarkers in breast cancer [ 33 , 34 ].…”

“…NGS developed the clinical methodology for genetic examination across various fields of medicine [ 34 ]. NGS can massively sequence millions of DNA reads, allowing for accurate characterization of the “status” of multiple genes; in this context, NGS-targeted gene sequencing enables the detection of driver mutations, which are responsible for progression and relapse and might be employed as predictive or prognostic biomarkers in breast cancer [ 33 , 34 ]. When compared to Sanger sequencing, NGS can offer doctors comparable genetic information at a cheaper cost and shorter time to results [ 2 , 34 ], yet the NGS limitations are the small read size and the difficulty in analyzing large alterations as structural variants.…”

“…NGS can massively sequence millions of DNA reads, allowing for accurate characterization of the “status” of multiple genes; in this context, NGS-targeted gene sequencing enables the detection of driver mutations, which are responsible for progression and relapse and might be employed as predictive or prognostic biomarkers in breast cancer [ 33 , 34 ]. When compared to Sanger sequencing, NGS can offer doctors comparable genetic information at a cheaper cost and shorter time to results [ 2 , 34 ], yet the NGS limitations are the small read size and the difficulty in analyzing large alterations as structural variants. Many studies employed the NGS as a technology in the detection of BRCA1/2 gene variants in various ethnic groups to implement the detection of gene variants using NGS in the routine line of diagnostics and may allow doctors to make more prompt and informed decisions about surgery or neo-adjuvant chemotherapy in breast cancer patients [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Trps1 predicts poor prognosis in advanced high grade serous ovarian carcinoma

“…As they lack the ability to repair DNA double-strand breaks by homologous recombination. 7 Targeting poly (ADP-ribose) polymerase (PARP) inhibitors against BRCA1/2 as maintenance therapy has been shown to improve clinical survival in patients with BRCA1/2 mutation and tumors lacking homologous recombination. 8,9 However, effective therapeutic targets remain elusive for the majority of cases.…”