Mutational Spectrum in a Worldwide Study of 29,700 Families with BRCA1 or BRCA2 Mutations

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Rebbeck Timothy R, Friebel Tara M, Friedman Eitan, Hamann Ute, Huo Dezheng, Kwong Ava, Olah Edith, Olopade Olufunmilayo I, Solano Angela R, Teo Soo-Hwang, Thomassen Mads, Weitzel Jeffrey N, Chan T L, Couch Fergus J, Goldgar David E, Kruse Torben A, Palmero Edenir Inêz, Park Sue Kyung, Torres Diana, van Rensburg Elizabeth J, Mcguffog Lesley, Parsons Michael T, Leslie Goska, Aalfs Cora M, Abugattas Julio, Adlard Julian, Agata Simona, Aittomäki Kristiina, Andrews Lesley, Andrulis Irene L, Arason Adalgeir, Arnold Norbert, Arun Banu K, Asseryanis Ella, Auerbach Leo, Azzollini Jacopo, Balmaña Judith, Barile Monica, Barkardottir Rosa B, Barrowdale Daniel, Benitez Javier, Berger Andreas, Berger Raanan, Blanco Amie M, Blazer Kathleen R, Blok Marinus J, Bonadona Valérie, Bonanni Bernardo, Bradbury Angela R, Brewer Carole, Buecher Bruno, Buys Saundra S, Caldes Trinidad, Caliebe Almuth, Caligo Maria A, Campbell Ian, Caputo Sandrine, Chiquette Jocelyne, Chung Wendy K, Claes Kathleen B M, Collée J Margriet, Cook Jackie, Davidson Rosemarie, de la Hoya Miguel, De Leeneer Kim, de Pauw Antoine, Delnatte Capucine, Diez Orland, Ding Yuan Chun, Ditsch Nina, Domchek Susan M, Dorfling Cecilia M, Velazquez Carolina, Dworniczak Bernd, Eason Jacqueline, Easton Douglas F, Eeles Ros, Ehrencrona Hans, Ejlertsen Bent, Engel Christoph, Engert Stefanie, Evans D Gareth, Faivre Laurence, Feliubadaló Lidia, Ferrer Sandra Fert, Foretova Lenka, Fowler Jeffrey, Frost Debra, Galvão Henrique C R, Ganz Patricia A, Garber Judy, Gauthier-Villars Marion, Gehrig Andrea, Gerdes Anne-Marie, Gesta Paul, Giannini Giuseppe, Giraud Sophie, Glendon Gord, Godwin Andrew K, Greene Mark H, Gronwald Jacek, Gutierrez-Barrera Angelica, Hahnen Eric, Hauke Jan, Henderson Alex, Hentschel Julia, Hogervorst Frans B L, Honisch Ellen, Imyanitov Evgeny N, Isaacs Claudine, Izatt Louise, Izquierdo Angel, Jakubowska Anna, James Paul, Janavicius Ramunas, Jensen Uffe Birk, John Esther M, Joseph Vijai, Kaczmarek Katarzyna, Karlan Beth Y, Kast Karin, Investigators Kconfab, Kim Sung-Won, Konstantopoulou Irene, Korach Jacob, Laitman Yael, Lasa Adriana, Lasset Christine, Lázaro Conxi, Lee Annette, Lee Min Hyuk, Lester Jenny, Lesueur Fabienne, Liljegren Annelie, Lindor Noralane M, Longy Michel, Loud Jennifer T, Lu Karen H, Lubinski Jan, Machackova Eva, Manoukian Siranoush, Mari Véronique, Martínez-Bouzas Cristina, Matrai Zoltan, Mebirouk Noura, Meijers-Heijboer Hanne E J, Meindl Alfons, Mensenkamp Arjen R, Mickys Ugnius, Miller Austin, Montagna Marco, Moysich Kirsten B, Mulligan Anna Marie, Musinsky Jacob, Neuhausen Susan L, Nevanlinna Heli, Ngeow Joanne, Nguyen Huu Phuc, Niederacher Dieter, Nielsen Henriette Roed, Nielsen Finn Cilius, Nussbaum Robert L, Offit Kenneth, Öfverholm Anna, Ong Kai-Ren, Osorio Ana, Papi Laura, Papp Janos, Pasini Barbara, Pedersen Inge Sokilde, Msc Ana Peixoto, Msc Nina Peruga, Peterlongo Paolo, Pohl Esther, Ba Nisha Pradhan, Prajzendanc Karolina, Prieur Fabienne, Pujol Pascal, Radice Paolo, Ramus Susan J, Rantala Johanna, Rashid Muhammad Usman, Rhiem Kerstin, Robson Mark, Rodriguez Gustavo C, Rogers Mark T, Rudaitis Vilius, Schmidt Ane Y, Schmutzler Rita Katharina, Senter Leigha, Shah Payal D, Sharma Priyanka, Side Lucy E, Simard Jacques, Singer Christian F, Skytte Anne-Bine, Slavin Thomas P, Snape Katie, Sobol Hagay, Southey Melissa, Steele Linda, Steinemann Doris, Sukiennicki Grzegorz, Sutter Christian, Szabo Csilla I, Tan Yen Y, Teixeira Manuel R, Terry Mary Beth, Teulé Alex, Thomas Abigail, Thull Darcy L, Tischkowitz Marc, Tognazzo Silvia, Toland Amanda Ewart, Topka Sabine, Trainer Alison H, Tung Nadine, van Asperen Christi J, van der Hout Annemieke H, van der Kolk Lizet E, van der Luijt Rob B, Van Heetvel
ISSN: 1098-1004

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on Caucasians 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 6 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. This article is protected by copyright. All rights reserved.

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