Dataset Information

Prevalence and Spectrum of BRCA Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study.

ABSTRACT: Hereditary breast and ovarian cancers are mainly linked to variants in BRCA1/2 genes. Recently, data has shown that identification of BRCA variants has an immediate impact not only in cancer prevention but also in targeted therapeutic approaches. This prospective observational study characterized the overall germline BRCA variant and variant of uncertain significance (VUS) frequency and spectrum in individuals affected by breast (BC) or ovarian cancer (OC) and in healthy individuals at risk by sequencing the entire BRCA genes. Of the 363 probands analyzed, 50 (13.8%) were BRCA1/2 mutated, 28 (7.7%) at BRCA1 and 23 (6.3%) at BRCA2 gene. The variant c.5266dupC p.(Gln1756Profs) was the most frequent alteration, representing 21.4% of the BRCA1 variants and 12.0% of all variants identified. The variant c.6313delA p.(Ile2105Tyrfs) of BRCA2 was the most frequent alteration observed in 6 patients. Interestingly, two new variants were identified in BRCA2. In addition, 25 different VUS were identified; two were reported for the first time in BRCA1 and two in BRCA2. The number of triple-negative BCs was significantly higher in patients with the pathogenic BRCA1/2-variant (36.4%) than in BRCA1/2 VUS (16.0%) and BRCA1/2 wild-type patients (10.7%) (p < 0.001). Our study reveals that the overall frequency of BRCA germline variants in the selected high-risk Italian population is about 13.8%. We believe that our results could have significant implications for preventive strategies for unaffected BRCA-carriers and effective targeted treatments such as PARP inhibitors for patients with BC or OC.

SUBMITTER: Foglietta J

PROVIDER: S-EPMC7464094 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Prevalence and Spectrum of BRCA Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study.

Foglietta Jennifer J Ludovini Vienna V Bianconi Fortunato F Pistola Lorenza L Reda Maria Sole MS Al-Refaie Antonella A Tofanetti Francesca Romana FR Mosconi Annamaria A Minenza Elisa E Anastasi Paola P Molica Carmen C Stracci Fabrizio F Roila Fausto F

Genes 20200812 8

Hereditary breast and ovarian cancers are mainly linked to variants in BRCA1/2 genes. Recently, data has shown that identification of BRCA variants has an immediate impact not only in cancer prevention but also in targeted therapeutic approaches. This prospective observational study characterized the overall germline BRCA variant and variant of uncertain significance (VUS) frequency and spectrum in individuals affected by breast (BC) or ovarian cancer (OC) and in healthy ind ...[more]

PMID: 32806537

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Project description:Breast cancer is a multifaceted disease that currently represents a leading cause of death in women worldwide. Over the past two decades (1998-2020), the National Health Laboratory Service's Human Genetics Laboratory in central South Africa screened more than 2,974 breast and/or ovarian cancer patients for abnormalities characteristic of the widely known familial breast cancer genes, Breast Cancer gene 1 (BRCA1) and Breast Cancer gene 2 (BRCA2). Patients were stratified according to the presence of family history, age at onset, stage of the disease, ethnicity and mutation status relative to BRCA1/2. Collectively, 481 actionable (likely-to pathogenic) variants were detected in this cohort among the different ethnic/racial groups. A combination of old (pre-2014) and new (post-2014) laboratory techniques was used to identify these variants. Additionally, targeted genotyping was performed as translational research revealed the first three recurrent South African pathogenic variants, namely BRCA1 c.1374del (legacy name 1493delC), BRCA1 c.2641G>T (legacy name E881X) and BRCA2 c.7934del (legacy name 8162delG). This initial flagship study resulted in a cost-effective diagnostic test that enabled screening of a particular ethnic group for these variants. Since then, various non-Afrikaner frequent variants were identified that were proven to represent recurrent variants. These include BRCA2 c.5771_5774del (legacy name 5999del4) and BRCA2 c.582G>A, both Black African founder mutations. By performing innovative translational research, medical science in South Africa can adopt first-world technologies into its healthcare context as a developing country. Over the past two decades, the progress made in the public sector enabled a pivotal shift away from population-directed genetic testing to the screening of potentially all breast and ovarian cancer patients, irrespective of ethnicity, family history or immunohistochemical status. The modifications over the years complied with international standards and guidelines aimed at universal healthcare for all. This article shares all the cohort stratifications and the likely-to pathogenic variants detected.

Dataset Information

Prevalence and Spectrum of BRCA Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study.

Publications

Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study.

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