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

作者：Timothy Richard Rebbeck, Tara M. Friebel, Eitan Friedman, Ute Hamann, Dezheng Huo, Ava Kwong, Edith Oláh, Olufunmilayo Ibironke Olopade, Angela Rosaria Solano, Soo‐Hwang Teo, Mads Thomassen, Jeffrey N. Weitzel, TL Chan, Fergus J. Couch, David E. Goldgar, Torben A. Kruse, Edenir Inêz Palmero, Sue K. Park, Diana Milena Torres, Elizabeth Jansen van Rensburg, Lesley McGuffog, Michael T. Parsons, Goska Leslie, Cora M. Aalfs, Julio E. Abugattas, Julian Adlard, Simona Agata, Kristiina Aittomäki, Lesley Andrews, Irene L. Andrulis, Aðalgeir Arason, Norbert Arnold, Banu K Arun, Ella Asseryanis, Leo Auerbach, Jacopo Azzollini, Judith Balmañà, Monica Barile, Rosa Bjork Barkardottir, Daniel Barrowdale, Javier J. Benitez, Andreas Berger, Raanan Berger, Amie M Blanco, Kathleen Reilly Blazer, Marinus J. Blok, Valérie Bonadona, Bernardo Bonanni, Angela R. Bradbury, Carole Brewer, Bruno Buecher, Saundra S. Buys, Trinidad Caldés, Almuth Caliebe, Maria Adelaide Caligo, Ian Campbell, Sandrine M. Caputo, Jocelyne Chiquette, Wendy K. Chung, Kathleen Claes, Johanna Margriet Collée, Jackie A Cook, Rosemarie Davidson, Miguel de la Hoya, Kim De Leeneer, Antoine De Pauw, Capucine Delnatte, Orland Dı́ez, Yuan Chun Ding, Nina Caroline Ditsch, Susan M. Domchek, Cecilia M. Dorfling, Carolina Velázquez, Bernd Dworniczak, Jacqueline Eason, Douglas F. Easton, Rosalind A. Eeles, Hans Ehrencrona, Bent Ejlertsen, EMBRACE, Christoph Engel, Stefanie Engert, D. Gareth Evans, Laurence Olivier Faivre, Lídia Feliubadaló, Sandra Fert Ferrer, Lenka Foretová, Jeffrey M. Fowler, Debra Frost, Henrique C.R. Galvão, Patricia A. Ganz, Judy Ellen Garber, Marion Gauthier‐Villars, Andrea Gehrig, GEMO Study Collaborators, Anne‐Marie Gerdes, Paul Gesta, Giuseppe Giannini, Sophie Giraud, Gord Glendon, Andrew K. Godwin, Mark H. Greene, Jacek Gronwald, Angelica M. Gutierrez‐Barrera, Eric Hahnen, Jan Hauke, HEBON, Alex Henderson, Julia Hentschel, Frans B.L. Hogervorst, Ellen Honisch, Evgeny N. Imyanitov, Claudine J. Isaacs, Louise Izatt, Á. Izquierdo, Anna Jakubowska, Paul Andrew James, Ramūnas Janavičius, Uffe Birk Jensen, Esther M. John, Joseph Vijai, Katarzyna Kaczmarek, Beth Y. Karlan, Karin Kast, kConFab Investigators, Sung-Won Kim, Irene Konstantopoulou, Jacob Korach, Yael Laitman, Adriana Lasa, Christine Lasset, Conxi Lázaro, Annette Lee, Min Hyuk Lee, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Noralane M. Lindor, Michel Longy, Jennifer T. Loud, Karen H. Lu, Jan Lubiński, Eva Macháčková, Siranoush Manoukian, Véronique Mari, Cristina Martínez-Bouzas, Zoltán Mátrai, Noura Mebirouk, Hanne E.J. Meijers-Heijboer, Alfons Meindl, Arjen R. Mensenkamp, Ugnius Mickys, Austin Miller, Marco Montagna, Kirsten B. Moysich, Anna Marie Mulligan, Jacob Musinsky, Susan L. Neuhausen, Heli A. Nevanlinna, Joanne Yuen Yie Ngeow, Huu Phuc Nguyen, Dieter Niederacher, Henriette Roed Nielsen, Finn C. Nielsen, Robert Luke Nussbaum, Kenneth Offit, Anna Öfverholm, Kai‐Ren Ong, Ana Osório, Laura Papi, J. Papp, Barbara Pasini, Inge Søkilde Pedersen, Ana Peixoto, Nina Peruga, Paolo Peterlongo, Esther Pohl, Nisha Pradhan, Karolina Prajzendanc, Fabienne Prieur, Pascal Pujol, Paolo Radice, Susan J. Ramus, Johanna Rantala, Muhammad Usman Rashid, Kerstin Rhiem, Mark E. Robson, Gustavo C. Rodriguez, Mark T. Rogers, Vilius Rudaitis, Ane Yde Schmidt, Rita Katharina Schmutzler, Leigha A. Senter, Payal Deepak Shah, Priyanka Sharma, Lucy E. Side, Jacques Simard, Christian Fridolin Singer, Anne‐Bine Skytte, Thomas Paul Slavin, Katie M.G. Snape, Hagay Sobol, Melissa C. Southey, Linda Roslyn Steele, Doris Steinemann, Grzegorz Sukiennicki, Christian Sutter, Csilla I. Szabo, Yen Y. Tan, Manuel Rodrigues Teixeira, Mary Beth Terry, Àlex Teulé, Abigail Thomas, Darcy L. Thull, Marc D. Tischkowitz, Silvia Tognazzo, Amanda Ewart Toland, Sabine Topka, Alison H. Trainer, Nadine Tung, Christi J. van Asperen, Annemieke H. van der Hout, Lizet E. van der Kolk, Rob B. van der Luijt, Mattias Van Heetvelde, Liliana Varesco, Raymonda Varon-Mateeva, Ana Isabel Vega, Cynthia Mayte Villarreal-Garza, Anna von Wachenfeldt, Lisa Walker, Shan Wang‐Gohrke, Barbara Wappenschmidt, Bernhard H. F. Weber, Drakoulis Yannoukakos, Sook-Yee Yoon, Cristina Zanzottera, Jamal Zidan, Kristin K. Zorn, Christina G. Selkirk, Peter J. Hulick, Georgia Chenevix‐Trench, Amanda B. Spurdle, Antonis C. Antoniou, Katherine L. Nathanson · 发表于：Human Mutation · 年份：2018 · DOI：10.1002/humu.23406 · 被引用次数：327 · 研究领域：BRCA gene mutations in cancer、CRISPR and Genetic Engineering、DNA Repair Mechanisms

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.