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Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families

Abstract

Genetic linkage data have shown that alterations of the BRCA1 gene are responsible for the majority of hereditary breast-ovarian cancers. However, BRCA1 germline mutations are found much less frequently than expected, especially as standard PCR-based mutation detection approaches focus on point and small gene alterations. In order to estimate the contribution of large gene rearrangements to the BRCA1 mutation spectrum, we have extensively analysed a series of 120 French breast-ovarian cancer cases. Thirty-eight were previously found carrier of a BRCA1 point mutation, 14 of a BRCA2 point mutation and one case has previously been reported as carrier of a large BRCA1 deletion. The remaining 67 cases were studied using the BRCA1 bar code approach on combed DNA which allows a panoramic view of the BRCA1 region. Three additional rearrangements were detected: a recurrent 23.8 kb deletion of exons 8–13, a 17.2 kb duplication of exons 3–8 and a 8.6 kb duplication of exons 18–20. Thus, in our series, BRCA1 large rearrangements accounted for 3.3% (4/120) of breast-ovarian cancer cases and 9.5% (4/42) of the BRCA1 gene mutation spectrum, suggesting that their screening is an important step that should be now systematically included in genetic testing surveys.

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References

  • Armour JAL, Sismani C, Patsali PC, Cross G . 2000 Nucleid. Acids Res. 28: 605–609

  • Barker DF, Liu X, Almeida ERA . 1996 Genomics 38: 215–222

  • Brown MA, Jones KA, Nicolai H, Bonjardim M, Black D, McFarlane R, De Jong P, Quirk JP, Lehrach H, Solomon E . 1995 Proc. Natl. Acad. Sci. USA 92: 4362–4366

  • Brown MA, Xu CF, Nicolai H, Griffiths B, Chambers JA, Black D, Solomon E . 1996 Oncogene 12: 2507–2513

  • Bruder CE, Hirvelä C, Tapia-Paez I, Fransson I, Segraves R, Hamilton G, Zhang XX, Evans DG, Wallace AJ, Baser ME, Zucman-Rossi J, Hergersberg M, Boltshauser E, Papi L, Rouleau GA, Poptodorov G, Jordanova A, Rask-Andersen H, Kluwe L, Mautner V, Sainio M, Hung G, Mathiesen T, Möller C, Pulst SM, Harder H, Heiberg A, Honda M, Niimura M, Sahlén S, Blennow E, Albertson DG, Pinkel D, Dumanski JP . 2001 Hum. Mol. Genet. 10: 271–282

  • Carson N, Gilpin C, Hunter A, Allanson J, Aubry H . 1999 Am. J. Hum. Genet. 65: A1610

  • Charbonnier F, Raux G, Wang Q, Drouot N, Cordier F, Limacher JM, Saurin JC, Puisieux A, Olschwang S, Frebourg T . 2000 Cancer Res. 60: 2760–2763

  • Claus EB, Risch N, Thompson WD . 1991 Am. J. Hum. Genet. 48: 232–242

  • Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BAJ, Gayther SA, Birch JM, Lindblom A, Stoppa-Lyonnet D, Bignon Y, Borg A, Hamann U, Haites N, Scott RJ, Maugard CM, Vasen H, Seitz S, Cannon-Albright LA, Schofield A, Zelada-Hedman M, the Breast Cancer Linkage Consortium . 1998 Am. J. Hum. Genet. 62: 676–689

  • Gad S, Aurias A, Puget N, Mairal A, Schurra C, Montagna M, Pages S, Caux V, Mazoyer S, Bensimon A, Stoppa-Lyonnet D . 2001a Genes Chrom. Cancer 31: 75–84

  • Gad S, Schuener M, Pages-Berhouet S, Caux-Moncoutier V, Bensimon A, Aurias A, Pinto M, Stoppa-Lyonnet D . 2001b J. Med. Genet. 38: 388–391

  • Laurendeau I, Bahuau M, Vodovar N, Larramendy C, Olivi M, Bieche Y, Vidaud M, Vidaud D . 1999 Clin. Chem. 45: 982–986

  • Michalet X, Ekong R, Fougerousse F, Rousseaux S, Schurra C, Hornigold N, van Slegtenhorst M, Wolfe J, Povey S, Beckmann JS, Bensimon A . 1997 Science 277: 1518–1523

  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A, Skolnick MH . 1994 Science 266: 66–71

  • Montagna M, Santancatterina M, Torri A, Menin C, Zullato D, Chieco-Bianchi L, D'Andrea E . 1999 Oncogene 18: 4160–4165

  • Nordling M, Karlsson P, Wahlstrom J, Engwall Y, Wallgren A, Martinsson T . 1998 Cancer Res. 58: 1372–1375

  • Pages S, Caux V, Stoppa-Lyonnet D, Tosi M . 2001 Br. J. Cancer 84: 482–488

  • Payne SR, Newman B, King MC . 2000 Genes Chromosomes Cancer 29: 58–62

  • Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drüsedau M, Hogervost FBL, Hageman S, Arts PJW, Ligtenberg MJL, Meijers-Heijboer H, Klijn JGM, Vasen HFA, Cornelisse CJ, van't Veer LJ, Bakker E, van Ommen GJB, Devilee P . 1997 Nat. Genet. 17: 341–345

  • Puget N, Torchard D, Serova-Sinilnikova O, Lynch HT, Feunteun J, Lenoir GM, Mazoyer S . 1997 Cancer Res. 57: 828–831

  • Puget N, Stoppa-Lyonnet D, Sinilnikova OM, Pages S, Lynch HT, Lenoir GM, Mazoyer S . 1999a Cancer Res. 59: 455–461

  • Puget N, Sinilnikova OM, Stoppa-Lyonnet D, Audoynaud C, Pages S, Lynch HT, Goldgar D, Lenoir GM, Mazoyer S . 1999b Am. J. Hum. Genet. 64: 300–302

  • Rohlfs EM, Puget N, Graham ML, Weber BL, Garber JE, Skrzynia C, Halperin JL, Lenoir GM, Silverman LM, Mazoyer S . 2000a Genes Chromosomes Cancer 28: 300–307

  • Rohlfs EM, Chung CH, Yang Q, Skrzynia C, Grody WW, Graham ML, Silverman LM . 2000b Hum. Genet. 107: 385–390

  • Serova O, Montagna M, Torchard D, Narod SA, Tonin P, Sylla B, Lynch HT, Feunteun J, Lenoir GM . 1996 Am. J. Hum. Genet. 58: 42–51

  • Smith TM, Lee MK, Szabo CI, Jerome N, McEuen M, Taylor M, Hood L, King MC . 1996 Genome Res. 6: 1029–1049

  • Stoppa-Lyonnet D, Puig PL, Essioux L, Pages S, Ithier G, Ligot L, Fourquet A, Salmon RJ, Clough KB, Pouillard P, the Institut Curie Breast Cancer Group Bonaiti-Pellie C, Thomas G . 1997 Am. J. Hum. Genet. 60: 1021–1030

  • Swensen J, Hoffman M, Skolnick MH, Neuhausen SL . 1997 Hum. Mol. Genet. 6: 1513–1517

  • The BRCA1 Exon 13 Duplication Screening Group. 2000 Am. J. Hum. Genet 67: 207–212

  • Unger MA, Nathanson KL, Calzone K, Antin-Ozerkis D, Shih HA, Martin A-M, Lenoir GM, Mazoyer S, Weber BL . 2000 Am. J. Hum. Genet. 67: 841–850

  • Wagner T, Stoppa-Lyonnet D, Fleischmann E, Muhr D, Pages S, Sandberg T, Caux V, Moeslinger R, Langbauer G, Borg A, Oefner P . 1999 Genomics 62: 369–376

  • Wang T, Lerer I, Gueta Z, Sagi M, Kadouri L, Peretz T, Abeliovich D . 2001 Genes Chromosomes Cancer 31: 91–95

  • Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G, Barfoot R, Hamoudi R, Patel S, Rice C, Biggs P, Hasim Y, Smith A, Connor F, Arason A, Gudmundsson J, Ficenec D, Kelsell I, Ford D, Tonin P, Bishop DT, Spurr NK, Ponder BAJ, Eeles R, Peto J, Devilee P, Cornelisse C, Lynch H, Narod S, Lenoir G, Egilsson V, Barkadottir RB, Easton DE, Bentley DR, Futreal PA, Ashworth A, Stratton MR . 1995 Nature 378: 789–792

  • Xu CF, Brown MA, Nicolai H, Chambers JA, Griffiths B, Solomon E . 1997 Hum. Mol. Genet. 6: 1057–1062

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Acknowledgements

We wish to thank the patients and their families for their cooperation. We gratefully acknowledge Isabelle Eugene and Sandrine Miglierina for their daily and efficient support in the organization of the genetic clinic. We wish to thank also Isabelle Lambert and Isabelle Bezier for the lymphoblastoid cell line establishment (Généthon, Evry). Thanks also to Stanislas Lyonnet and Mario Tosi for critical reading of the manuscript. This work was supported by the Institut Curie ‘Programme Incitatif et Coopératif: Génétique et Biologie des Cancers du Sein’ and the Ligue Nationale Contre le Cancer (A Aurias). S Gad is supported by a fellowship from the Association pour la Recherche contre le Cancer.

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Correspondence to Dominique Stoppa-Lyonnet.

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Gad, S., Caux-Moncoutier, V., Pagès-Berhouet, S. et al. Significant contribution of large BRCA1 gene rearrangements in 120 French breast and ovarian cancer families. Oncogene 21, 6841–6847 (2002). https://doi.org/10.1038/sj.onc.1205685

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