Skip to main content

Advertisement

SpringerLink
Log in

Rare germline large rearrangements in the BRCA1/2 genes and eight candidate genes in 472 patients with breast cancer predisposition

  • Brief Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Hereditary breast cancers account for up to 5–10 % of breast cancers and a majority are related to the BRCA1 and BRCA2 genes. However, many families with breast cancer predisposition do not carry any known mutations for BRCA1 and BRCA2 genes. We explored the incidence of rare large rearrangements in the coding, noncoding and flanking regions of BRCA1/2 and in eight other candidate genes—CHEK2, BARD1, ATM, RAD50, RAD51, BRIP1, RAP80 and PALB2. A dedicated zoom-in CGH-array was applied to screen for rearrangements in 472 unrelated French individuals from breast-ovarian cancer families that were being followed in eight French oncogenetic laboratories. No new rearrangement was found neither in the genomic regions of BRCA1/2 nor in candidate genes, except for the CHEK2 and BARD1 genes. Three heterozygous deletions were detected in the 5′ and 3′ flanking regions of BRCA1. One large deletion introducing a frameshift was identified in the CHEK2 gene in two families and one heterozygous deletion was detected within an intron of BARD1. The study demonstrates the usefulness of CGH-array in routine genetic analysis and, aside from the CHEK2 rearrangements, indicates there is a very low incidence of large rearrangements in BRCA1/2 and in the other eight candidate genes in families already explored for BRCA1/2 mutations. Finally, next-generation sequencing should bring new information about point mutations in intronic and flanking regions and also medium size rearrangements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Claus EB, Risch N, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48(2):232–242

    PubMed  CAS  Google Scholar 

  2. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130. doi:10.1086/375033

    Article  PubMed  CAS  Google Scholar 

  3. Chan KY, Liu W, Long JR, Yip SP, Chan SY, Shu XO, Chua DT, Cheung AN, Ching JC, Cai H, Au GK, Chan M, Foo W, Ngan HY, Gao YT, Ngan ES, Garcia-Barcelo MM, Zheng W, Khoo US (2009) Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women. J Med Genet 46(1):32–39. doi:10.1136/jmg.2007.057174

    Article  PubMed  CAS  Google Scholar 

  4. Lheureux S, Lambert B, Krieger S, Legros A, Vaur D, Denoyelle C, Berthet P, Poulain L, Hardouin A (2011) Two novel variants in the 3′ UTR of the BRCA1 gene in familial breast and/or ovarian cancer. Breast Cancer Res Treat 125(3):885–891. doi:10.1007/s10549-010-1165-8

    Article  PubMed  CAS  Google Scholar 

  5. Whiley PJ, Guidugli L, Walker LC, Healey S, Thompson BA, Lakhani SR, Da Silva LM, Tavtigian SV, Goldgar DE, Brown MA, Couch FJ, Spurdle AB (2011) Splicing and multifactorial analysis of intronic BRCA1 and BRCA2 sequence variants identifies clinically significant splicing aberrations up to 12 nucleotides from the intron/exon boundary. Hum Mutat 32(6):678–687. doi:10.1002/humu.21495

    Article  PubMed  CAS  Google Scholar 

  6. Sluiter MD, van Rensburg EJ (2011) Large genomic rearrangements of the BRCA1 and BRCA2 genes: review of the literature and report of a novel BRCA1 mutation. Breast Cancer Res Treat 125(2):325–349. doi:10.1007/s10549-010-0817-z

    Article  PubMed  CAS  Google Scholar 

  7. Mazoyer S (2005) Genomic rearrangements in the BRCA1 and BRCA2 genes. Hum Mutat 25(5):415–422

    Article  PubMed  CAS  Google Scholar 

  8. Coulet F, Pires F, Rouleau E, Lefol C, Martin S, Colas C, Cohen-Haguenauer O, Giurgea I, Fajac A, Nogues C, Demange L, Hardouin A, Lidereau R, Soubrier F (2010) A one-step prescreening for point mutations and large rearrangement in BRCA1 and BRCA2 genes using quantitative polymerase chain reaction and high-resolution melting curve analysis. Genet Test Mol Biomark 14(5):677–690. doi:10.1089/gtmb.2009.0183

    Article  CAS  Google Scholar 

  9. Lim YK, Lau PT, Ali AB, Lee SC, Wong JE, Putti TC, Sng JH (2007) Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet 71(4):331–342. doi:10.1111/j.1399-0004.2007.00773.x

    Article  PubMed  CAS  Google Scholar 

  10. Agata S, Dalla Palma M, Callegaro M, Scaini MC, Menin C, Ghiotto C, Nicoletto O, Zavagno G, Chieco-Bianchi L, D’Andrea E, Montagna M (2005) Large genomic deletions inactivate the BRCA2 gene in breast cancer families. J Med Genet 42(10):e64

    Article  PubMed  CAS  Google Scholar 

  11. Walsh T, Lee MK, Casadei S, Thornton AM, Stray SM, Pennil C, Nord AS, Mandell JB, Swisher EM, King MC (2010) Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci USA 107(28):12629–12633. doi:10.1073/pnas.1007983107

    Article  PubMed  CAS  Google Scholar 

  12. Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King MC, Swisher EM (2011) Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci USA 108(44):18032–18037. doi:10.1073/pnas.1115052108

    Article  PubMed  CAS  Google Scholar 

  13. Walsh T, King MC (2007) Ten genes for inherited breast cancer. Cancer Cell 11(2):103–105

    Article  PubMed  CAS  Google Scholar 

  14. Zhang B, Beeghly-Fadiel A, Long J, Zheng W (2011) Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol 12(5):477–488. doi:10.1016/S1470-2045(11)70076-6

    Article  PubMed  CAS  Google Scholar 

  15. CHEK2 Breast Cancer Case-Control Consortium (2004) CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet 74(6):1175–1182

    Google Scholar 

  16. Walsh T, Casadei S, Coats KH, Swisher E, Stray SM, Higgins J, Roach KC, Mandell J, Lee MK, Ciernikova S, Foretova L, Soucek P, King MC (2006) Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA 295(12):1379–1388

    Article  PubMed  CAS  Google Scholar 

  17. Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N (2006) ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38(8):873–875

    Article  PubMed  CAS  Google Scholar 

  18. Tommiska J, Seal S, Renwick A, Barfoot R, Baskcomb L, Jayatilake H, Bartkova J, Tallila J, Kaare M, Tamminen A, Heikkila P, Evans DG, Eccles D, Aittomaki K, Blomqvist C, Bartek J, Stratton MR, Nevanlinna H, Rahman N (2006) Evaluation of RAD50 in familial breast cancer predisposition. Int J Cancer 118(11):2911–2916

    Article  PubMed  CAS  Google Scholar 

  19. Jakubowska A, Gronwald J, Menkiszak J, Gorski B, Huzarski T, Byrski T, Edler L, Lubinski J, Scott RJ, Hamann U (2007) The RAD51 135 G>C polymorphism modifies breast cancer and ovarian cancer risk in Polish BRCA1 mutation carriers. Cancer Epidemiol Biomark Prev 16(2):270–275

    Article  CAS  Google Scholar 

  20. Antoniou AC, Sinilnikova OM, Simard J, Leone M, Dumont M, Neuhausen SL, Struewing JP, Stoppa-Lyonnet D, Barjhoux L, Hughes DJ, Coupier I, Belotti M, Lasset C, Bonadona V, Bignon YJ, Rebbeck TR, Wagner T, Lynch HT, Domchek SM, Nathanson KL, Garber JE, Weitzel J, Narod SA, Tomlinson G, Olopade OI, Godwin A, Isaacs C, Jakubowska A, Lubinski J, Gronwald J, Gorski B, Byrski T, Huzarski T, Peock S, Cook M, Baynes C, Murray A, Rogers M, Daly PA, Dorkins H, Schmutzler RK, Versmold B, Engel C, Meindl A, Arnold N, Niederacher D, Deissler H, Spurdle AB, Chen X, Waddell N, Cloonan N, Kirchhoff T, Offit K, Friedman E, Kaufmann B, Laitman Y, Galore G, Rennert G, Lejbkowicz F, Raskin L, Andrulis IL, Ilyushik E, Ozcelik H, Devilee P, Vreeswijk MP, Greene MH, Prindiville SA, Osorio A, Benitez J, Zikan M, Szabo CI, Kilpivaara O, Nevanlinna H, Hamann U, Durocher F, Arason A, Couch FJ, Easton DF, Chenevix-Trench G (2007) RAD51 135G→C modifies breast cancer risk among BRCA2 mutation carriers: results from a combined analysis of 19 studies. Am J Hum Genet 81(6):1186–1200

    Article  PubMed  CAS  Google Scholar 

  21. Kato M, Yano K, Matsuo F, Saito H, Katagiri T, Kurumizaka H, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Nagawa H, Nakamura Y, Miki Y (2000) Identification of Rad51 alteration in patients with bilateral breast cancer. J Hum Genet 45(3):133–137. doi:10.1007/s100380050199

    Article  PubMed  CAS  Google Scholar 

  22. De Nicolo A, Tancredi M, Lombardi G, Flemma CC, Barbuti S, Di Cristofano C, Sobhian B, Bevilacqua G, Drapkin R, Caligo MA (2008) A novel breast cancer-associated BRIP1 (FANCJ/BACH1) germ-line mutation impairs protein stability and function. Clin Cancer Res 14(14):4672–4680. doi:10.1158/1078-0432.CCR-08-0087

    Article  PubMed  Google Scholar 

  23. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR (2007) PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 39(2):165–167

    Article  PubMed  CAS  Google Scholar 

  24. Stacey SN, Sulem P, Johannsson OT, Helgason A, Gudmundsson J, Kostic JP, Kristjansson K, Jonsdottir T, Sigurdsson H, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Bergthorsson JT, Amundadottir LT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2006) The BARD1 Cys557Ser variant and breast cancer risk in Iceland. PLoS Med 3(7):e217. doi:10.1371/journal.pmed.0030217

    Article  PubMed  Google Scholar 

  25. De Brakeleer S, De Greve J, Loris R, Janin N, Lissens W, Sermijn E, Teugels E (2010) Cancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families. Hum Mutat 31(3):E1175–E1185. doi:10.1002/humu.21200

    Article  PubMed  Google Scholar 

  26. Akbari MR, Ghadirian P, Robidoux A, Foumani M, Sun Y, Royer R, Zandvakili I, Lynch H, Narod SA (2009) Germline RAP80 mutations and susceptibility to breast cancer. Breast Cancer Res Treat 113(2):377–381. doi:10.1007/s10549-008-9938-z

    Article  PubMed  CAS  Google Scholar 

  27. Nikkila J, Coleman KA, Morrissey D, Pylkas K, Erkko H, Messick TE, Karppinen SM, Amelina A, Winqvist R, Greenberg RA (2009) Familial breast cancer screening reveals an alteration in the RAP80 UIM domain that impairs DNA damage response function. Oncogene 28(16):1843–1852. doi:10.1038/onc.2009.33

    Article  PubMed  CAS  Google Scholar 

  28. Ferla R, Calo V, Cascio S, Rinaldi G, Badalamenti G, Carreca I, Surmacz E, Colucci G, Bazan V, Russo A (2007) Founder mutations in BRCA1 and BRCA2 genes. Ann Oncol 18(Suppl 6):vi93–vi98. doi:10.1093/annonc/mdm234

    Article  PubMed  Google Scholar 

  29. Sabatier R, Adelaide J, Finetti P, Ferrari A, Huiart L, Sobol H, Chaffanet M, Birnbaum D, Bertucci F (2010) BARD1 homozygous deletion, a possible alternative to BRCA1 mutation in basal breast cancer. Genes Chromosomes Cancer 49(12):1143–1151. doi:10.1002/gcc.20822

    Article  PubMed  CAS  Google Scholar 

  30. Cavalieri S, Funaro A, Pappi P, Migone N, Gatti RA, Brusco A (2008) Large genomic mutations within the ATM gene detected by MLPA, including a duplication of 41 kb from exon 4 to 20. Ann Hum Genet 72(Pt 1):10–18. doi:10.1111/j.1469-1809.2007.00399.x

    PubMed  CAS  Google Scholar 

  31. Cavalieri S, Funaro A, Porcedda P, Turinetto V, Migone N, Gatti RA, Brusco A (2006) ATM mutations in Italian families with ataxia telangiectasia include two distinct large genomic deletions. Hum Mutat 27(10):1061. doi:10.1002/humu.9454

    Article  PubMed  Google Scholar 

  32. Blanco A, de la Hoya M, Balmana J, Ramon YCT, Teule A, Miramar MD, Esteban E, Infante M, Benitez J, Torres A, Tejada MI, Brunet J, Grana B, Balbin M, Perez-Segura P, Osorio A, Velasco EA, Chirivella I, Calvo MT, Feliubadalo L, Lasa A, Diez O, Carracedo A, Caldes T, Vega A (2011) Detection of a large rearrangement in PALB2 in Spanish breast cancer families with male breast cancer. Breast Cancer Res Treat. doi:10.1007/s10549-011-1842-2

    Google Scholar 

  33. Rouleau E, Lefol C, Tozlu S, Andrieu C, Guy C, Copigny F, Nogues C, Bieche I, Lidereau R (2007) High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1. Clin Genet 72(3):199–207

    Article  PubMed  CAS  Google Scholar 

  34. Staaf J, Torngren T, Rambech E, Johansson U, Persson C, Sellberg G, Tellhed L, Nilbert M, Borg A (2008) Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH). Hum Mutat 29(4):555–564

    Article  PubMed  CAS  Google Scholar 

  35. Caux-Moncoutier V, Pages-Berhouet S, Michaux D, Asselain B, Castera L, De Pauw A, Buecher B, Gauthier-Villars M, Stoppa-Lyonnet D, Houdayer C (2009) Impact of BRCA1 and BRCA2 variants on splicing: clues from an allelic imbalance study. Eur J Hum Genet 17(11):1471–1480

    Google Scholar 

  36. Barrois M, Bieche I, Mazoyer S, Champeme MH, Bressac-de Paillerets B, Lidereau R (2004) Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families. Clin Genet 65(2):131–136

    Article  PubMed  CAS  Google Scholar 

  37. Rouleau E, Lefol C, Moncoutier V, Castera L, Houdayer C, Caputo S, Bieche I, Buisson M, Mazoyer S, Stoppa-Lyonnet D, Nogues C, Lidereau R (2010) A missense variant within BRCA1 exon 23 causing exon skipping. Cancer Genet Cytogenet 202(2):144–146. doi:10.1016/j.cancergencyto.2010.07.122

    Article  PubMed  CAS  Google Scholar 

  38. Kuusisto KM, Bebel A, Vihinen M, Schleutker J, Sallinen SL (2011) Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals. Breast Cancer Res 13(1):R20. doi:10.1186/bcr2832

    Article  PubMed  CAS  Google Scholar 

  39. Matsuzaki H, Wang PH, Hu J, Rava R, Fu GK (2009) High resolution discovery and confirmation of copy number variants in 90 Yoruba Nigerians. Genome Biol 10(11):R125. doi:10.1186/gb-2009-10-11-r125

    Article  PubMed  Google Scholar 

  40. Desrichard A, Bidet Y, Uhrhammer N, Bignon YJ (2011) CHEK2 germline mutation contribution to hereditary breast cancer in non-BRCA-mutated families. Breast Cancer Res 13(6):R119. doi:10.1186/bcr3062

    Article  PubMed  CAS  Google Scholar 

  41. Tuohy TM, Done MW, Lewandowski MS, Shires PM, Saraiya DS, Huang SC, Neklason DW, Burt RW (2010) Large intron 14 rearrangement in APC results in splice defect and attenuated FAP. Hum Genet 127(3):359–369. doi:10.1007/s00439-009-0776-9

    Article  PubMed  CAS  Google Scholar 

  42. Li L, Cohen M, Wu J, Sow MH, Nikolic B, Bischof P, Irminger-Finger I (2007) Identification of BARD1 splice-isoforms involved in human trophoblast invasion. Int J Biochem Cell Biol 39(9):1659–1672. doi:10.1016/j.biocel.2007.04.018

    Article  PubMed  CAS  Google Scholar 

  43. Li L, Ryser S, Dizin E, Pils D, Krainer M, Jefford CE, Bertoni F, Zeillinger R, Irminger-Finger I (2007) Oncogenic BARD1 isoforms expressed in gynecological cancers. Cancer Res 67(24):11876–11885. doi:10.1158/0008-5472.CAN-07-2370

    Article  PubMed  CAS  Google Scholar 

  44. Ryser S, Dizin E, Jefford CE, Delaval B, Gagos S, Christodoulidou A, Krause KH, Birnbaum D, Irminger-Finger I (2009) Distinct roles of BARD1 isoforms in mitosis: full-length BARD1 mediates Aurora B degradation, cancer-associated BARD1beta scaffolds Aurora B and BRCA2. Cancer Res 69(3):1125–1134. doi:10.1158/0008-5472.CAN-08-2134

    Article  PubMed  CAS  Google Scholar 

  45. Tsuzuki M, Wu W, Nishikawa H, Hayami R, Oyake D, Yabuki Y, Fukuda M, Ohta T (2006) A truncated splice variant of human BARD1 that lacks the RING finger and ankyrin repeats. Cancer Lett 233(1):108–116. doi:10.1016/j.canlet.2005.03.012

    Article  PubMed  CAS  Google Scholar 

  46. Brown MA, Lo LJ, Catteau A, Xu CF, Lindeman GJ, Hodgson S, Solomon E (2002) Germline BRCA1 promoter deletions in UK and Australian familial breast cancer patients: identification of a novel deletion consistent with BRCA1:psiBRCA1 recombination. Hum Mutat 19(4):435–442. doi:10.1002/humu.10055

    Article  PubMed  CAS  Google Scholar 

  47. Benko S, Fantes JA, Amiel J, Kleinjan DJ, Thomas S, Ramsay J, Jamshidi N, Essafi A, Heaney S, Gordon CT, McBride D, Golzio C, Fisher M, Perry P, Abadie V, Ayuso C, Holder-Espinasse M, Kilpatrick N, Lees MM, Picard A, Temple IK, Thomas P, Vazquez MP, Vekemans M, Roest Crollius H, Hastie ND, Munnich A, Etchevers HC, Pelet A, Farlie PG, Fitzpatrick DR, Lyonnet S (2009) Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nat Genet 41(3):359–364. doi:10.1038/ng.329

    Article  PubMed  CAS  Google Scholar 

  48. Dowty JG, Lose F, Jenkins MA, Chang JH, Chen X, Beesley J, Dite GS, Southey MC, Byrnes GB, Tesoriero A, Giles GG, Hopper JL, Spurdle AB (2008) The RAD51D E233G variant and breast cancer risk: population-based and clinic-based family studies of Australian women. Breast Cancer Res Treat 112(1):35–39. doi:10.1007/s10549-007-9832-0

    Article  PubMed  CAS  Google Scholar 

  49. Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, Bowden G, Kalmyrzaev B, Warren-Perry M, Snape K, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Eccles D, Evans DG, Renwick A, Seal S, Lord CJ, Ashworth A, Reis-Filho JS, Antoniou AC, Rahman N (2011) Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet 43(9):879–882. doi:10.1038/ng.893ng.893

    Article  PubMed  CAS  Google Scholar 

  50. Wong MW, Nordfors C, Mossman D, Pecenpetelovska G, Avery-Kiejda KA, Talseth-Palmer B, Bowden NA, Scott RJ (2011) BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast Cancer Res Treat 127(3):853–859. doi:10.1007/s10549-011-1443-0

    Article  PubMed  CAS  Google Scholar 

  51. Romero A, Perez-Segura P, Tosar A, Garcia-Saenz JA, Diaz-Rubio E, Caldes T, de la Hoya M (2011) A HRM-based screening method detects RAD51C germ-line deleterious mutations in Spanish breast and ovarian cancer families. Breast Cancer Res Treat. doi:10.1007/s10549-011-1543-x

    Google Scholar 

  52. Zheng Y, Zhang J, Hope K, Niu Q, Huo D, Olopade OI (2010) Screening RAD51C nucleotide alterations in patients with a family history of breast and ovarian cancer. Breast Cancer Res Treat 124(3):857–861. doi:10.1007/s10549-010-1095-5

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Association d’Aide à la Recherche Cancérologique de Saint-Cloud (ARCS) and the Ligue against Cancer Haut-de-Seine 92.

Conflict of Interest

None.

Author information

Authors and Affiliations

  1. Laboratoire d’Oncogénétique, Institut Curie—Hôpital René Huguenin, 35 rue Dailly, 92210, Saint-Cloud, France

    E. Rouleau, A. Briaux, S. Caputo, I. Bieche & R. Lidereau

  2. IMAXIO Biopôle Clermont-Limagne, Saint-Beauzire, France

    B. Jesson & V. Chabaud

  3. Service d’Oncogénétique Clinique, Institut Curie—Hôpital René Huguenin, Saint-Cloud, France

    C. Nogues & L. Demange

  4. Laboratoire de Génétique Constitutionnelle—Unité Inserm U916 VINCO, Institut Bergonié, Bordeaux Cedex, France

    E. Barouk-Simonet & F. Bonnet

  5. Plateforme Mixte de Génétique Constitutionnelle des Cancers Fréquents—Institut Paoli-Calmettes, Marseille, France

    V. Bourdon

  6. Service de Génétique, Institut Curie et Université Paris Descartes, Paris, France

    L. Castera & D. Stoppa-Lyonnet

  7. Laboratoire d’Oncogénétique et Angiogénétique Moléculaire, Groupe Hospitalier Pitié-Salpêtriere, Assistance Publique-Hopitaux de Paris, Université Pierre et Marie Curie, Paris, France

    F. Coulet

  8. Service de Génétique Médicale, Unité de Génétique Moléculaire, CHU Nantes, Nantes, France

    C. Delnatte

  9. Laboratoire de Biologie Oncologique, Institut Jean-Godinot, Reims, France

    C. Delvincourt

  10. Laboratoire d’Oncologie Moléculaire Humaine, Centre Oscar Lambret, Lille, France

    J. Fournier & J. P. Peyrat

  11. Laboratoire d’Oncologie Moléculaire—Centre François Baclesse, Caen, France

    A. Hardouin

  12. IMAXIO Biopôle Clermont-Limagne, Saint-Beauzire, France

    V. Vidal

  13. Laboratoire de Biologie Tumorale—Oncogénétique—Centre Paul Strauss, Strasbourg, France

    D. Muller

  14. Laboratoire de Génétique Médicale, CHU Nancy Brabois, 2 rue du Morvan, 54511, Vandoeuvre lès Nancy, France

    J. Sokolowska & M. Bronner

  15. Laboratoire d’Oncogénétique, CRCT, INSERM U1037, Team «Tumor Radioresistance: from Signalling Pathways to Clinical Trials», Institut Claudius Regaud, Toulouse, France

    C. Toulas

  16. Département d’oncogénétique, Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, Clermont-Ferrand, France

    Y. J. Bignon & N. Uhrhammer

Authors
  1. E. Rouleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Jesson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Briaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Nogues
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. Chabaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Demange
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Sokolowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F. Coulet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Barouk-Simonet
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Y. J. Bignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F. Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. V. Bourdon
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. Bronner
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S. Caputo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L. Castera
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. C. Delnatte
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. C. Delvincourt
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. J. Fournier
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. A. Hardouin
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. D. Muller
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. J. P. Peyrat
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. C. Toulas
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. N. Uhrhammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. V. Vidal
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. D. Stoppa-Lyonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. I. Bieche
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. R. Lidereau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Rouleau.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 39 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rouleau, E., Jesson, B., Briaux, A. et al. Rare germline large rearrangements in the BRCA1/2 genes and eight candidate genes in 472 patients with breast cancer predisposition. Breast Cancer Res Treat 133, 1179–1190 (2012). https://doi.org/10.1007/s10549-012-2009-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-012-2009-5

Keywords

Search

Navigation