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

Rebbeck, Timothy R. ; Friebel, Tara M. ; Friedman, Eitan ; Hamann, Ute ; Huo, Dezheng ; Kwong, Ava ; Olah, Edith ; Olopade, Olufunmilayo I. ; Solano, Angela R. and Teo, Soo Hwang , et al. (2018) In Human Mutation 39(5). p.593-620
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,... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
BRCA1, BRCA2, Breast cancer, Ethnicity, Geography, Mutation, Ovarian cancer
in
Human Mutation
volume
39
issue
5
pages
593 - 620
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85043494756
  • pmid:29446198
ISSN
1059-7794
DOI
10.1002/humu.23406
language
English
LU publication?
no
id
218700c9-460e-4869-8f41-75a4abdde40a
date added to LUP
2018-03-23 12:58:14
date last changed
2024-11-13 02:53:15
@article{218700c9-460e-4869-8f41-75a4abdde40a,
  abstract     = {{<p>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.</p>}},
  author       = {{Rebbeck, Timothy R. and Friebel, Tara M. and Friedman, Eitan and Hamann, Ute and Huo, Dezheng and Kwong, Ava and Olah, Edith and Olopade, Olufunmilayo I. and Solano, Angela R. and Teo, Soo Hwang and Thomassen, Mads and Weitzel, Jeffrey N. and Chan, Tl and Couch, Fergus J. and Goldgar, David E. and Kruse, Torben A. and Palmero, Edenir Inêz and Park, Sue Kyung and Torres, Diana and van Rensburg, Elizabeth J. and Mcguffog, Lesley and Parsons, Michael T. and Leslie, Goska and Aalfs, Cora M. and Abugattas, Julio and Adlard, Julian and Agata, Simona and Aittomäki, Kristiina and Andrews, Lesley and Andrulis, Irene L. and Arason, Adalgeir and Arnold, Norbert and Arun, Banu K. and Asseryanis, Ella and Auerbach, Leo and Azzollini, Jacopo and Balmaña, Judith and Barile, Monica and Barkardottir, Rosa B. and Barrowdale, Daniel and Benitez, Javier and Berger, Andreas and Berger, Raanan and Blanco, Amie M. and Blazer, Kathleen R. and Blok, Marinus J. and Bonadona, Valérie and Bonanni, Bernardo and Bradbury, Angela R. and Brewer, Carole and Buecher, Bruno and Buys, Saundra S. and Caldes, Trinidad and Caliebe, Almuth and Caligo, Maria A. and Campbell, Ian and Caputo, Sandrine M. and Chiquette, Jocelyne and Chung, Wendy K. and Claes, Kathleen B.M. and Collée, J. Margriet and Cook, Jackie and Davidson, Rosemarie and de la Hoya, Miguel and De Leeneer, Kim and de Pauw, Antoine and Delnatte, Capucine and Diez, Orland and Ding, Yuan Chun and Ditsch, Nina and Domchek, Susan M. and Dorfling, Cecilia M. and Velazquez, Carolina and Dworniczak, Bernd and Eason, Jacqueline and Easton, Douglas F. and Eeles, Ros and Ehrencrona, Hans and Ejlertsen, Bent and Engel, Christoph and Engert, Stefanie and Evans, D. Gareth and Faivre, Laurence and Feliubadaló, Lidia and Ferrer, Sandra Fert and Foretova, Lenka and Fowler, Jeffrey and Frost, Debra and Galvão, Henrique C.R. and Ganz, Patricia A. and Garber, Judy and Gauthier-Villars, Marion and Gehrig, Andrea and Gerdes, Anne Marie and Gesta, Paul and Giannini, Giuseppe and Giraud, Sophie and Glendon, Gord and Godwin, Andrew K. and Greene, Mark H. and Gronwald, Jacek and Gutierrez-Barrera, Angelica and Hahnen, Eric and Hauke, Jan and Henderson, Alex and Hentschel, Julia and Hogervorst, Frans B.L. and Honisch, Ellen and Imyanitov, Evgeny N. and Isaacs, Claudine and Izatt, Louise and Izquierdo, Angel and Jakubowska, Anna and James, Paul and Janavicius, Ramunas and Jensen, Uffe Birk and John, Esther M. and Vijai, Joseph and Kaczmarek, Katarzyna and Karlan, Beth Y. and Kast, Karin and Kim, Sung Won and Konstantopoulou, Irene and Korach, Jacob and Laitman, Yael and Lasa, Adriana and Lasset, Christine and Lázaro, Conxi and Lee, Annette and Lee, Min Hyuk and Lester, Jenny and Lesueur, Fabienne and Liljegren, Annelie and Lindor, Noralane M. and Longy, Michel and Loud, Jennifer T. and Lu, Karen H. and Lubinski, Jan and Machackova, Eva and Manoukian, Siranoush and Mari, Véronique and Martínez-Bouzas, Cristina and Matrai, Zoltan and Mebirouk, Noura and Meijers-Heijboer, Hanne E.J. and Meindl, Alfons and Mensenkamp, Arjen R. and Mickys, Ugnius and Miller, Austin and Montagna, Marco and Moysich, Kirsten B. and Mulligan, Anna Marie and Musinsky, Jacob and Neuhausen, Susan L. and Nevanlinna, Heli and Ngeow, Joanne and Nguyen, Huu Phuc and Niederacher, Dieter and Nielsen, Henriette Roed and Nielsen, Finn Cilius and Nussbaum, Robert L. and Offit, Kenneth and Öfverholm, Anna and Ong, Kai ren and Osorio, Ana and Papi, Laura and Papp, Janos and Pasini, Barbara and Pedersen, Inge Sokilde and Msc, Ana Peixoto and Msc, Nina Peruga and Peterlongo, Paolo and Pohl, Esther and Ba, Nisha Pradhan and Prajzendanc, Karolina and Prieur, Fabienne and Pujol, Pascal and Radice, Paolo and Ramus, Susan J. and Rantala, Johanna and Rashid, Muhammad Usman and Rhiem, Kerstin and Robson, Mark and Rodriguez, Gustavo C. and Rogers, Mark T. and Rudaitis, Vilius and Schmidt, Ane Y. and Schmutzler, Rita Katharina and Senter, Leigha and Shah, Payal D. and Sharma, Priyanka and Side, Lucy E. and Simard, Jacques and Singer, Christian F. and Skytte, Anne Bine and Slavin, Thomas P. and Snape, Katie and Sobol, Hagay and Southey, Melissa and Steele, Linda and Steinemann, Doris and Sukiennicki, Grzegorz and Sutter, Christian and Szabo, Csilla I. and Tan, Yen Y. and Teixeira, Manuel R. and Terry, Mary Beth and Teulé, Alex and Thomas, Abigail and Thull, Darcy L. and Tischkowitz, Marc and Tognazzo, Silvia and Toland, Amanda Ewart and Topka, Sabine and Trainer, Alison H. and Tung, Nadine and van Asperen, Christi J. and van der Hout, Annemieke H. and van der Kolk, Lizet E. and van der Luijt, Rob B. and Van Heetvelde, Mattias and Varesco, Liliana and Varon-Mateeva, Raymonda and Vega, Ana and Villarreal-Garza, Cynthia and von Wachenfeldt, Anna and Walker, Lisa and Wang-Gohrke, Shan and Wappenschmidt, Barbara and Weber, Bernhard H.F. and Yannoukakos, Drakoulis and Yoon, Sook Yee and Zanzottera, Cristina and Zidan, Jamal and Zorn, Kristin K. and Hutten Selkirk, Christina G. and Hulick, Peter J. and Chenevix-Trench, Georgia and Spurdle, Amanda B. and Antoniou, Antonis C. and Nathanson, Katherine L.}},
  issn         = {{1059-7794}},
  keywords     = {{BRCA1; BRCA2; Breast cancer; Ethnicity; Geography; Mutation; Ovarian cancer}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{593--620}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Human Mutation}},
  title        = {{Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations}},
  url          = {{http://dx.doi.org/10.1002/humu.23406}},
  doi          = {{10.1002/humu.23406}},
  volume       = {{39}},
  year         = {{2018}},
}