Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations Journal Article


Authors: Rebbeck, T. R.; Friebel, T. M.; Friedman, E.; Hamann, U.; Huo, D.; Kwong, A.; Olah, E.; Olopade, O. I.; Solano, A. R.; Teo, S. H.; Thomassen, M.; Weitzel, J. N.; Chan, T. L.; Couch, F. J.; Goldgar, D. E.; Kruse, T. A.; Palmero, E. I.; Park, S. K.; Torres, D.; van Rensburg, E. J.; McGuffog, L.; Parsons, M. T.; Leslie, G.; Aalfs, C. M.; Abugattas, J.; Adlard, J.; Agata, S.; Aittomäki, K.; Andrews, L.; Andrulis, I. L.; Arason, A.; Arnold, N.; Arun, B. K.; Asseryanis, E.; Auerbach, L.; Azzollini, J.; Balmaña, J.; Barile, M.; Barkardottir, R. B.; Barrowdale, D.; Benitez, J.; Berger, A.; Berger, R.; Blanco, A. M.; Blazer, K. R.; Blok, M. J.; Bonadona, V.; Bonanni, B.; Bradbury, A. R.; Brewer, C.; Buecher, B.; Buys, S. S.; Caldes, T.; Caliebe, A.; Caligo, M. A.; Campbell, I.; Caputo, S. M.; Chiquette, J.; Chung, W. K.; Claes, K. B. M.; Collée, J. M.; Cook, J.; Davidson, R.; de la Hoya, M.; De Leeneer, K.; de Pauw, A.; Delnatte, C.; Diez, O.; Ding, Y. C.; Ditsch, N.; Domchek, S. M.; Dorfling, C. M.; Velazquez, C.; Dworniczak, B.; Eason, J.; Easton, D. F.; Eeles, R.; Ehrencrona, H.; Ejlertsen, B.; EMBRACE; Engel, C.; Engert, S.; Evans, D. G.; Faivre, L.; Feliubadaló, L.; Ferrer, S. F.; Foretova, L.; Fowler, J.; Frost, D.; Galvão, H. C. R.; Ganz, P. A.; Garber, J.; Gauthier-Villars, M.; Gehrig, A.; GEMO Study Collaborators; Gerdes, A. M.; Gesta, P.; Giannini, G.; Giraud, S.; Glendon, G.; Godwin, A. K.; Greene, M. H.; Gronwald, J.; Gutierrez-Barrera, A.; Hahnen, E.; Hauke, J.; HEBON; Henderson, A.; Hentschel, J.; Hogervorst, F. B. L.; Honisch, E.; Imyanitov, E. N.; Isaacs, C.; Izatt, L.; Izquierdo, A.; Jakubowska, A.; James, P.; Janavicius, R.; Jensen, U. B.; John, E. M.; Vijai, J.; Kaczmarek, K.; Karlan, B. Y.; Kast, K.; KConFab Investigators; Kim, S. W.; Konstantopoulou, I.; Korach, J.; Laitman, Y.; Lasa, A.; Lasset, C.; Lázaro, C.; Lee, A.; Lee, M. H.; Lester, J.; Lesueur, F.; Liljegren, A.; Lindor, N. M.; Longy, M.; Loud, J. T.; Lu, K. H.; Lubinski, J.; Machackova, E.; Manoukian, S.; Mari, V.; Martínez-Bouzas, C.; Matrai, Z.; Mebirouk, N.; Meijers-Heijboer, H. E. J.; Meindl, A.; Mensenkamp, A. R.; Mickys, U.; Miller, A.; Montagna, M.; Moysich, K. B.; Mulligan, A. M.; Musinsky, J.; Neuhausen, S. L.; Nevanlinna, H.; Ngeow, J.; Nguyen, H. P.; Niederacher, D.; Nielsen, H. R.; Nielsen, F. C.; Nussbaum, R. L.; Offit, K.; Öfverholm, A.; Ong, K. R.; Osorio, A.; Papi, L.; Papp, J.; Pasini, B.; Pedersen, I. S.; Peixoto, A.; Peruga, N.; Peterlongo, P.; Pohl, E.; Pradhan, N.; Prajzendanc, K.; Prieur, F.; Pujol, P.; Radice, P.; Ramus, S. J.; Rantala, J.; Rashid, M. U.; Rhiem, K.; Robson, M.; Rodriguez, G. C.; Rogers, M. T.; Rudaitis, V.; Schmidt, A. Y.; Schmutzler, R. K.; Senter, L.; Shah, P. D.; Sharma, P.; Side, L. E.; Simard, J.; Singer, C. F.; Skytte, A. B.; Slavin, T. P.; Snape, K.; Sobol, H.; Southey, M.; Steele, L.; Steinemann, D.; Sukiennicki, G.; Sutter, C.; Szabo, C. I.; Tan, Y. Y.; Teixeira, M. R.; Terry, M. B.; Teulé, A.; Thomas, A.; Thull, D. L.; Tischkowitz, M.; Tognazzo, S.; Toland, A. E.; Topka, S.; Trainer, A. H.; Tung, N.; van Asperen, C. J.; van der Hout, A. H.; van der Kolk, L. E.; van der Luijt, R. B.; Van Heetvelde, M.; Varesco, L.; Varon-Mateeva, R.; Vega, A.; Villarreal-Garza, C.; von Wachenfeldt, A.; Walker, L.; Wang-Gohrke, S.; Wappenschmidt, B.; Weber, B. H. F.; Yannoukakos, D.; Yoon, S. Y.; Zanzottera, C.; Zidan, J.; Zorn, K. K.; Hutten Selkirk, C. G.; Hulick, P. J.; Chenevix-Trench, G.; Spurdle, A. B.; Antoniou, A. C.; Nathanson, K. L.
Article Title: Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
Abstract: The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations. © 2018 Wiley Periodicals, Inc.
Keywords: mutation; ovarian cancer; breast cancer; brca1; brca2; ethnicity; geography
Journal Title: Human Mutation
Volume: 39
Issue: 5
ISSN: 1059-7794
Publisher: Wiley Liss  
Date Published: 2018-05-01
Start Page: 593
End Page: 620
Language: English
DOI: 10.1002/humu.23406
PROVIDER: scopus
PMCID: PMC5903938
PUBMED: 29446198
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    495 Offit
  2. Mark E Robson
    358 Robson
  3. Vijai Joseph
    113 Joseph
  4. Sabine   Topka
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