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

EMBRACE

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)593-620
Number of pages28
JournalHuman Mutation
Volume39
Issue number5
DOIs
Publication statusPublished - May 2018

Cite this

@article{ba4557810b584da7a00ce555e66e3ce4,
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.",
author = "EMBRACE and Rebbeck, {Timothy R} and Friebel, {Tara M} and Eitan Friedman and Ute Hamann and Dezheng Huo and Ava Kwong and Edith Olah and Olopade, {Olufunmilayo I} and Solano, {Angela R} and Soo-Hwang Teo and Mads Thomassen and Weitzel, {Jeffrey N} and Chan, {T L} and Couch, {Fergus J} and Goldgar, {David E} and Kruse, {Torben A} and Palmero, {Edenir In{\^e}z} and Park, {Sue Kyung} and Diana Torres and {van Rensburg}, {Elizabeth J} and Lesley McGuffog and Parsons, {Michael T} and Goska Leslie and Aalfs, {Cora M} and Julio Abugattas and Julian Adlard and Simona Agata and Kristiina Aittom{\"a}ki and Lesley Andrews and Andrulis, {Irene L} and Adalgeir Arason and Norbert Arnold and Arun, {Banu K} and Ella Asseryanis and Leo Auerbach and Jacopo Azzollini and Judith Balma{\~n}a and Monica Barile and Barkardottir, {Rosa B} and Daniel Barrowdale and Javier Benitez and Andreas Berger and Raanan Berger and Blanco, {Amie M} and Blazer, {Kathleen R} and Blok, {Marinus J} and Val{\'e}rie Bonadona and Bernardo Bonanni and Coll{\'e}e, {J Margriet} and Meijers-Heijboer, {Hanne E J}",
note = "{\circledC} 2018 Wiley Periodicals, Inc.",
year = "2018",
month = "5",
doi = "10.1002/humu.23406",
language = "English",
volume = "39",
pages = "593--620",
journal = "Human Mutation",
issn = "1059-7794",
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Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. / EMBRACE.

In: Human Mutation, Vol. 39, No. 5, 05.2018, p. 593-620.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

AU - EMBRACE

AU - Rebbeck, Timothy R

AU - Friebel, Tara M

AU - Friedman, Eitan

AU - Hamann, Ute

AU - Huo, Dezheng

AU - Kwong, Ava

AU - Olah, Edith

AU - Olopade, Olufunmilayo I

AU - Solano, Angela R

AU - Teo, Soo-Hwang

AU - Thomassen, Mads

AU - Weitzel, Jeffrey N

AU - Chan, T L

AU - Couch, Fergus J

AU - Goldgar, David E

AU - Kruse, Torben A

AU - Palmero, Edenir Inêz

AU - Park, Sue Kyung

AU - Torres, Diana

AU - van Rensburg, Elizabeth J

AU - McGuffog, Lesley

AU - Parsons, Michael T

AU - Leslie, Goska

AU - Aalfs, Cora M

AU - Abugattas, Julio

AU - Adlard, Julian

AU - Agata, Simona

AU - Aittomäki, Kristiina

AU - Andrews, Lesley

AU - Andrulis, Irene L

AU - Arason, Adalgeir

AU - Arnold, Norbert

AU - Arun, Banu K

AU - Asseryanis, Ella

AU - Auerbach, Leo

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Barile, Monica

AU - Barkardottir, Rosa B

AU - Barrowdale, Daniel

AU - Benitez, Javier

AU - Berger, Andreas

AU - Berger, Raanan

AU - Blanco, Amie M

AU - Blazer, Kathleen R

AU - Blok, Marinus J

AU - Bonadona, Valérie

AU - Bonanni, Bernardo

AU - Collée, J Margriet

AU - Meijers-Heijboer, Hanne E J

N1 - © 2018 Wiley Periodicals, Inc.

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

U2 - 10.1002/humu.23406

DO - 10.1002/humu.23406

M3 - Article

VL - 39

SP - 593

EP - 620

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 5

ER -