Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study
Hereditary breast and ovarian cancers are mainly linked to variants in <i>BRCA1</i>/2 genes. Recently, data has shown that identification of <i>BRCA</i> variants has an immediate impact not only in cancer prevention but also in targeted therapeutic approaches. This prospectiv...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/8/925 |
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| author | Jennifer Foglietta Vienna Ludovini Fortunato Bianconi Lorenza Pistola Maria Sole Reda Antonella Al-Refaie Francesca Romana Tofanetti Annamaria Mosconi Elisa Minenza Paola Anastasi Carmen Molica Fabrizio Stracci Fausto Roila |
| author_facet | Jennifer Foglietta Vienna Ludovini Fortunato Bianconi Lorenza Pistola Maria Sole Reda Antonella Al-Refaie Francesca Romana Tofanetti Annamaria Mosconi Elisa Minenza Paola Anastasi Carmen Molica Fabrizio Stracci Fausto Roila |
| author_sort | Jennifer Foglietta |
| collection | DOAJ |
| description | Hereditary breast and ovarian cancers are mainly linked to variants in <i>BRCA1</i>/2 genes. Recently, data has shown that identification of <i>BRCA</i> variants has an immediate impact not only in cancer prevention but also in targeted therapeutic approaches. This prospective observational study characterized the overall germline <i>BRCA</i> 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 <i>BRCA</i> genes. Of the 363 probands analyzed, 50 (13.8%) were <i>BRCA1/2</i> mutated, 28 (7.7%) at <i>BRCA1</i> and 23 (6.3%) at <i>BRCA2</i> gene. The variant c.5266dupC p.(Gln1756Profs) was the most frequent alteration, representing 21.4% of the <i>BRCA1</i> variants and 12.0% of all variants identified. The variant c.6313delA p.(Ile2105Tyrfs) of <i>BRCA2</i> was the most frequent alteration observed in 6 patients. Interestingly, two new variants were identified in <i>BRCA2</i>. In addition, 25 different VUS were identified; two were reported for the first time in <i>BRCA1</i> and two in <i>BRCA2</i>. The number of triple-negative BCs was significantly higher in patients with the pathogenic <i>BRCA1/2</i>-variant (36.4%) than in <i>BRCA1/2</i> VUS (16.0%) and <i>BRCA1/2</i> wild-type patients (10.7%) (<i>p</i> < 0.001). Our study reveals that the overall frequency of <i>BRCA</i> 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 <i>BRCA</i>-carriers and effective targeted treatments such as PARP inhibitors for patients with BC or OC. |
| first_indexed | 2024-03-10T17:35:39Z |
| format | Article |
| id | doaj.art-86b753d70b4c4080a513dd355a10fad0 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T17:35:39Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-86b753d70b4c4080a513dd355a10fad02023-11-20T09:52:16ZengMDPI AGGenes2073-44252020-08-0111892510.3390/genes11080925Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric StudyJennifer Foglietta0Vienna Ludovini1Fortunato Bianconi2Lorenza Pistola3Maria Sole Reda4Antonella Al-Refaie5Francesca Romana Tofanetti6Annamaria Mosconi7Elisa Minenza8Paola Anastasi9Carmen Molica10Fabrizio Stracci11Fausto Roila12Medical Oncology Division, S. Maria Hospital, 05100 Terni, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyUmbria Cancer Registry, University of Perugia, 06129 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyDepartment of Experimental Medicine, Public Health Section, University of Perugia, 06129 Perugia, ItalyMedical Oncology Division, S. Maria della Misericordia Hospital, 06132 Perugia, ItalyHereditary breast and ovarian cancers are mainly linked to variants in <i>BRCA1</i>/2 genes. Recently, data has shown that identification of <i>BRCA</i> variants has an immediate impact not only in cancer prevention but also in targeted therapeutic approaches. This prospective observational study characterized the overall germline <i>BRCA</i> 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 <i>BRCA</i> genes. Of the 363 probands analyzed, 50 (13.8%) were <i>BRCA1/2</i> mutated, 28 (7.7%) at <i>BRCA1</i> and 23 (6.3%) at <i>BRCA2</i> gene. The variant c.5266dupC p.(Gln1756Profs) was the most frequent alteration, representing 21.4% of the <i>BRCA1</i> variants and 12.0% of all variants identified. The variant c.6313delA p.(Ile2105Tyrfs) of <i>BRCA2</i> was the most frequent alteration observed in 6 patients. Interestingly, two new variants were identified in <i>BRCA2</i>. In addition, 25 different VUS were identified; two were reported for the first time in <i>BRCA1</i> and two in <i>BRCA2</i>. The number of triple-negative BCs was significantly higher in patients with the pathogenic <i>BRCA1/2</i>-variant (36.4%) than in <i>BRCA1/2</i> VUS (16.0%) and <i>BRCA1/2</i> wild-type patients (10.7%) (<i>p</i> < 0.001). Our study reveals that the overall frequency of <i>BRCA</i> 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 <i>BRCA</i>-carriers and effective targeted treatments such as PARP inhibitors for patients with BC or OC.https://www.mdpi.com/2073-4425/11/8/925<i>BRCA1/2</i> variant carrierbreast cancerVUSgenetic testingrisk evaluation |
| spellingShingle | Jennifer Foglietta Vienna Ludovini Fortunato Bianconi Lorenza Pistola Maria Sole Reda Antonella Al-Refaie Francesca Romana Tofanetti Annamaria Mosconi Elisa Minenza Paola Anastasi Carmen Molica Fabrizio Stracci Fausto Roila Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study Genes <i>BRCA1/2</i> variant carrier breast cancer VUS genetic testing risk evaluation |
| title | Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study |
| title_full | Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study |
| title_fullStr | Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study |
| title_full_unstemmed | Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study |
| title_short | Prevalence and Spectrum of <i>BRCA</i> Germline Variants in Central Italian High Risk or Familial Breast/Ovarian Cancer Patients: A Monocentric Study |
| title_sort | prevalence and spectrum of i brca i germline variants in central italian high risk or familial breast ovarian cancer patients a monocentric study |
| topic | <i>BRCA1/2</i> variant carrier breast cancer VUS genetic testing risk evaluation |
| url | https://www.mdpi.com/2073-4425/11/8/925 |
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