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. 2020 May 19;12(5):1286.
doi: 10.3390/cancers12051286.

Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome

Concetta Santonocito  1   2 , Roberta Rizza  1   2 , Ida Paris  3 , Laura De Marchis  4 , Carmela Paolillo  5 , Giordana Tiberi  4 , Giovanni Scambia  3 , Ettore Capoluongo  6   7
Affiliations

Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome

Concetta Santonocito et al. Cancers (Basel). .

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.

Keywords: BRCA1/2; next-generation sequencing; novel variants.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Variant spectrum in BRCA1 and BRCA2 genes. Histograms indicate the absolute number of all variants in BRCA1 and BRCA2, identified in our population.
Figure 2
Figure 2
Lollipop plots showing the distribution of novel BRCA1 variants (a) and BRCA2 (b) identified in our patients’ group. The plots were obtained by the informatic tool Mutation Mapper—cBioPortal for Cancer Genomics (GenBank Reference BRCA1: NM_007300 and GenBank Reference BRCA2: NM_000059).
Figure 3
Figure 3
The histograms represent the absolute number of patients divided by BC, OC, BC/OC, carrier or other that show a variant located within one of the classic domains of the BRCA1 (a) or BRCA2 (b) genes.
Figure 4
Figure 4
BRCA1 and BRCA2 cluster regions: (a) the classic regions of the BRCA1 gene are shown within the rectangle, while the putative domains, identified by black lines, immediately below. The different putative regions are identified by black lines; (b) the classic regions of the BRCA2 gene are shown within the rectangle, while the putative domains, identified by black lines, immediately below.
See this image and copyright information in PMC

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