Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?
The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and r...
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doaj-cac8d726c1844e4888e0c6376ae275192021-06-01T01:36:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01225832583210.3390/ijms22115832Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?Roberta Zuntini0Elena Bonora1Laura Maria Pradella2Laura Benedetta Amato3Michele Vidone4Sara De Fanti5Irene Catucci6Laura Cortesi7Veronica Medici8Simona Ferrari9Giuseppe Gasparre10Paolo Peterlongo11Marco Sazzini12Daniela Turchetti13Center for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, ItalyIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, ItalyDepartment of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41125 Modena, ItalyDepartment of Oncology and Hematology, Azienda Ospedaliero Universitaria di Modena, 41125 Modena, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, 20139 Milan, ItalyDepartment of Biological, Geological and Environmental Sciences, University of Bologna, 40126 Bologna, ItalyCenter for Studies on Hereditary Cancer, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, ItalyThe NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels.https://www.mdpi.com/1422-0067/22/11/5832hereditary breast cancerNBNnibrinvariants |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roberta Zuntini Elena Bonora Laura Maria Pradella Laura Benedetta Amato Michele Vidone Sara De Fanti Irene Catucci Laura Cortesi Veronica Medici Simona Ferrari Giuseppe Gasparre Paolo Peterlongo Marco Sazzini Daniela Turchetti |
spellingShingle |
Roberta Zuntini Elena Bonora Laura Maria Pradella Laura Benedetta Amato Michele Vidone Sara De Fanti Irene Catucci Laura Cortesi Veronica Medici Simona Ferrari Giuseppe Gasparre Paolo Peterlongo Marco Sazzini Daniela Turchetti Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? International Journal of Molecular Sciences hereditary breast cancer NBN nibrin variants |
author_facet |
Roberta Zuntini Elena Bonora Laura Maria Pradella Laura Benedetta Amato Michele Vidone Sara De Fanti Irene Catucci Laura Cortesi Veronica Medici Simona Ferrari Giuseppe Gasparre Paolo Peterlongo Marco Sazzini Daniela Turchetti |
author_sort |
Roberta Zuntini |
title |
Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? |
title_short |
Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? |
title_full |
Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? |
title_fullStr |
Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? |
title_full_unstemmed |
Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next? |
title_sort |
detecting variants in the nbn gene while testing for hereditary breast cancer: what to do next? |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-05-01 |
description |
The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels. |
topic |
hereditary breast cancer NBN nibrin variants |
url |
https://www.mdpi.com/1422-0067/22/11/5832 |
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