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

被引：224

作者：

Rebbeck, Timothy R. ^{[1
]}

Friebel, Tara M. ^{[1
]}

Friedman, Eitan ^{[2
,3
]}

Hamann, Ute ^{[4
]}

Huo, Dezheng ^{[5
]}

Kwong, Ava ^{[6
]}

Olah, Edith ^{[7
]}

Olopade, Olufunmilayo I. ^{[5
]}

Solano, Angela R. ^{[8
,9
]}

Teo, Soo-Hwang ^{[10
]}

Thomassen, Mads ^{[11
]}

Weitzel, Jeffrey N. ^{[12
]}

Chan, T. L. ^{[13
]}

Couch, Fergus J. ^{[14
]}

Goldgar, David E. ^{[15
]}

Kruse, Torben A. ^{[11
]}

Palmero, Edenir Inez ^{[16
]}

Park, Sue Kyung ^{[17
,18
,19
]}

Torres, Diana ^{[4
,20
]}

van Rensburg, Elizabeth J. ^{[21
]}

McGuffog, Lesley ^{[22
]}

Parsons, Michael T. ^{[23
]}

Leslie, Goska ^{[22
]}

Aalfs, Cora M. ^{[24
]}

Abugattas, Julio ^{[25
]}

Adlard, Julian ^{[26
]}

Agata, Simona ^{[27
]}

Aittomaki, Kristiina ^{[28
]}

Andrews, Lesley ^{[29
]}

Andrulis, Irene L. ^{[30
,31
]}

Arason, Adalgeir ^{[40
,41
]}

Arnold, Norbert ^{[32
]}

Arun, Banu K. ^{[33
,34
]}

Asseryanis, Ella ^{[35
,36
]}

Auerbach, Leo ^{[35
,36
]}

Azzollini, Jacopo ^{[37
]}

Balmana, Judith ^{[38
]}

Barile, Monica ^{[39
]}

Barkardottir, Rosa B. ^{[40
,41
]}

Barrowdale, Daniel ^{[22
]}

Benitez, Javier ^{[42
,43
,44
]}

Berger, Andreas ^{[45
]}

Berger, Raanan ^{[46
]}

Blanco, Amie M. ^{[47
]}

Blazer, Kathleen R. ^{[12
]}

Blok, Marinus J. ^{[48
]}

Bonadona, Valerie ^{[49
]}

Bonanni, Bernardo ^{[39
]}

Bradbury, Angela R. ^{[50
]}

Brewer, Carole ^{[51
]}

机构：

[1] Harvard TH Chan Sch Publ Hlth, Boston, MA USA

[2] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel

[3] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[4] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany

[5] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA

[6] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China

[7] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary

[8] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina

[9] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina

[10] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia

[11] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark

[12] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA

[13] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China

[14] Dept Lab Med & Pathol, Rochester, MN USA

[15] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA

[16] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil

[17] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea

[18] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea

[19] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea

[20] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia

[21] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa

[22] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[23] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia

[24] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

[25] City Hope Clin Canc Genom Community Res Network, Duarte, CA USA

[26] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England

[27] Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy

[28] Helsinki Univ Hosp, Dept Clin Genet, Helsinki, Finland

[29] Prince Wales Hosp, Hereditary Canc Clin, Randwick, NSW, Australia

[30] Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[31] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[32] Med Univ Vienna, Dept Gynaecol & Oncol, Vienna, Austria

[33] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[34] Univ Texas MD Anderson Canc Ctr, Clin Canc Genet Program, Houston, TX 77030 USA

[35] Med Univ Vienna, Dept OB GYN, Vienna, Austria

[36] Med Univ Vienna, Comprehens Canc Ctr, Vienna, Austria

[37] Fdn IRCCS Ist Ricovero & Cura Carattere Sci Inst, Dept Med Oncol & Hematol, Unit Med Genet, Milan, Italy

[38] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain

[39] IEO, Div Canc Prevent & Genet, Milan, Italy

[40] Landspitali LSH V Hringbraut, Lab Cell Biol, Dept Pathol, Hus 9, IS-101 Reykjavik, Iceland

[41] Univ Iceland, Fac Med, BMC Biomed Ctr, Reykjavik, Iceland

[42] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain

[43] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Genotyping Unit CEGEN, Madrid, Spain

[44] Biomed Network Rare Dis CIBERER, Madrid, Spain

[45] Med Univ Vienna, Comprehens Canc Ctr, Dept OB GYN, Vienna, Austria

[46] Chaim Sheba Med Ctr, Inst Oncol, Ramat Gan, Israel

[47] UCSF Canc Genet & Prevent Program, San Francisco, CA USA

[48] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands

[49] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, 28 Rue Laennec, Lyon, France

[50] Univ Penn, Dept Med, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA

来源：

HUMAN MUTATION | 2018年 / 39卷 / 05期

关键词：

BRCA1; BRCA2; breast cancer; ethnicity; geography; mutation; ovarian cancer; BREAST-CANCER PATIENTS; GERMLINE MUTATIONS; FOUNDER MUTATIONS; HIGH-RISK; HAPLOTYPE ANALYSIS; HEREDITARY BREAST; PHENOTYPE ANALYSIS; 185DELAG MUTATION; RECURRENT BRCA1; GENE-MUTATIONS;

D O I：

10.1002/humu.23406

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：593 / 620

页数：28

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