Abstract
Pathogenic variants (PVs) carriers in BRCA1 or BRCA2 are associated with an elevated lifetime risk of developing breast cancer (BC) and/or ovarian cancer (OC). The prevalence of BRCA1 and BRCA2 germline alterations is extremely variable among different ethnic groups. Particularly, the rate of variants in Italian BC and/or OC families is rather controversial and ranges from 8% to 37%, according to different reports. By In Vitro Diagnostic (IVD) next generation sequencing (NGS)-based pipelines, we routinely screened thousands of patients with either sporadic or cancer family history. By NGS, we identified new PVs and some variants of uncertain significance (VUS) which were also evaluated in silico using dedicated tools. We report in detail data regarding BRCA1/2 variants identified in 517 out of 2351 BC and OC patients. The aim of this study was to report the incidence and spectrum of BRCA1/2 variants observed in BC and/or OC patients, tested in at Policlinico Gemelli Foundation Hospital, the origin of which is mainly from Central and Southern Italy. This study provides an overview of the variant frequency in these geographic areas of Italy and provides data that could be used in the clinical management of patients.
Highlights
The BRCA1 and BRCA2 are two genes involved in double-strand DNA breaks repair by the homologous recombination system (HR)
The present paper shows that the BRCA1/2 variants are distributed along the entire sequence, with a higher frequency for BRCA2 than BRCA1: we identified 103 BRCA1 and 181 BRCA2 deleterious variants
This study is the first report about the landscape of germline BRCA1 and BRCA2 Pathogenic variants (PVs) in a large cohort of patients affected by breast and ovarian cancer coming from the Central–South Italy, where, as recently published by Capoluongo et al [59], it is quite probable to identify founder variants in subjects belonging to apparently unrelated families
Summary
The BRCA1 and BRCA2 are two genes involved in double-strand DNA breaks repair by the homologous recombination system (HR). Pathogenic variants (PVs) in one of these genes, causing the absence or dysfunction of the BRCA proteins, can dramatically impair HR resulting in genomic instability. These PVs are deleterious and increase an individual’s likelihood of developing cancer [1,2,3,4]. Deleterious germline PV carriers in BRCA1 or BRCA2 have an elevated lifetime risk of developing breast and/or ovarian cancer, 60–80% for breast cancer (BC) and Cancers 2020, 12, 1286; doi:10.3390/cancers12051286 www.mdpi.com/journal/cancers. PVs in these genes can be involved in a higher risk of developing prostate cancer [7] and pancreatic cancer [8]. The variants are classified and interpreted according to both the ACMG (American College of Medical Genetics) indications [9]
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