The contribution of germline rearrangements to the spectrum of BRCA2 mutations
| العنوان: | The contribution of germline rearrangements to the spectrum of BRCA2 mutations |
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| المؤلفون: | Dominique Stoppa-Lyonnet, Isabelle Tournier, Thierry Frebourg, T.D. N’Guyen, Mario Tosi, Florence Coulet, Agnès Hardouin, Sylvie Mazoyer, C Capoulade-Metay, Danielle Muller, Valérie Bonadona, Rosette Lidereau, Christophe Philippe, Alain Lortholary, Florent Soubrier, Federica Casilli, Philippe Maillet, Catherine Noguès, Laurence Gladieff, Hagay Sobol, Catherine Dugast, Christine Maugard, Agnès Chompret, Christine Toulas, Stéphane Bézieau, Violaine Bourdon, Pierre O. Chappuis, Diane Provencher, Jean-Pierre Fricker, Claude Houdayer, Laurence Faivre, Paul Gesta, Pascaline Berthet, Olga M. Sinilnikova, C. Delvincourt |
| المساهمون: | Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2006, 43, pp.e49-e49 Journal of Medical Genetics, 2006, 43, pp.e49-e49 |
| بيانات النشر: | BMJ, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], medicine.medical_specialty, endocrine system diseases, Genetic counseling, Genes, BRCA2, Biology, Polymerase Chain Reaction, Germline, Exon, Breast cancer, Germline mutation, Molecular genetics, Genetics, medicine, Humans, skin and connective tissue diseases, Gene, Germ-Line Mutation, Genetics (clinical), Sequence Deletion, Exons, Middle Aged, medicine.disease, Molecular biology, female genital diseases and pregnancy complications, Male breast cancer, Female, Online Mutation Report |
| الوصف: | Background: Few germline BRCA2 rearrangements have been described compared with the large number of germline rearrangements reported in the BRCA1 gene. However, some BRCA2 rearrangements have been reported in families that included at least one case of male breast cancer. Objective: To estimate the contribution of large genomic rearrangements to the spectrum of BRCA2 defects. Methods: Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the BRCA2 gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions/duplications in many genes including BRCA1 and BRCA2 . Results: We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of ⩽50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. BRCA2 mutations were detected in 18.6% (36 index cases) and BRCA1 mutations in 12.4% (24 index cases) of these families. Of the 134 BRCA1/2 negative index cases in this subgroup, 120 were screened for large rearrangements of BRCA2 using QMPSF. Novel and distinct BRCA2 deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the BRCA2 mutation spectrum. Conclusion: The molecular diagnosis of breast cancer predisposition should include screening for BRCA2 rearrangements, at least in families with a high probability of BRCA2 defects. |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4acc701f98f5c834d4a7520d2e7ae21dTest https://doi.org/10.1136/jmg.2005.040212Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4acc701f98f5c834d4a7520d2e7ae21d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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