Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
Timothy Rebbeck
,
Tara Friebel
,
Eitan Friedman
,
Ute Hamann
,
Dezheng Huo
,
Ava Kwong
,
Edith Olah
,
Olufunmilayo Olopade
,
Angela Solano
,
Soo-Hwang Teo
,
Mads Thomassen
,
Jeffrey Weitzel
,
Tl Chan
,
Fergus Couch
,
David E. Goldgar
,
Torben A. Kruse
,
Edenir Inêz Palmero
,
Sue Kyung Park
,
Diana Torres
,
Elizabeth Jansen van Rensburg
,
Lesley Mcguffog
,
Michael Parsons
,
Goska Leslie
,
Cora Aalfs
,
Julio Abugattas
,
Julian Adlard
,
Simona Agata
,
Kristiina Aittomäki
,
Lesley Andrews
,
Irene Andrulis
,
Adalgeir Arason
,
Norbert Arnold
,
Banu Arun
,
Ella Asseryanis
,
Leo Auerbach
,
Jacopo Azzollini
,
Judith Balmaña
,
Monica Barile
,
Rosa Barkardottir
,
Daniel Barrowdale
,
Javier Benitez
,
Andreas Berger
,
Raanan Berger
,
Amie Blanco
,
Kathleen Blazer
,
Marinus Blok
,
Valérie Bonadona
(1)
,
Bernardo Bonanni
,
Angela Bradbury
,
Carole Brewer
,
Bruno Buecher
(2)
,
Saundra Buys
,
Trinidad Caldés
,
Almuth Caliebe
,
Maria Adelaide Caligo
,
Ian Campbell
,
Sandrine Caputo
(2)
,
Jocelyne Chiquette
,
Wendy Chung
,
Kathleen Claes
,
J Margriet Collée
,
Jackie Cook
,
Rosemarie Davidson
,
Miguel de La Hoya
,
Kim de Leeneer
,
Antoine de Pauw
(2)
,
Capucine Delnatte
(3)
,
Orland Diez
,
Yuan Chun Ding
,
Nina Ditsch
,
Susan Domchek
,
Cecilia Dorfling
,
Carolina Velazquez
,
Bernd Dworniczak
,
Jacqueline Eason
,
Douglas F. Easton
,
Ros Eeles
,
Hans Ehrencrona
,
Bent Ejlertsen
,
Christoph Engel
,
Stefanie Engert
,
D Gareth Evans
,
Laurence Faivre
(4, 5)
,
Lídia Feliubadaló
,
Sandra Fert Ferrer
(6)
,
Lenka Foretova
,
Jeffrey Fowler
,
Debra Frost
,
Henrique Galvão
,
Patricia Ganz
,
Judy Garber
,
Marion Gauthier-Villars
(2)
,
Andrea Gehrig
,
Anne-Marie Gerdes
,
Paul Gesta
(7)
,
Giuseppe Giannini
,
Sophie Giraud
(1)
,
Gord Glendon
,
Andrew Godwin
,
Mark Greene
,
Jacek Gronwald
,
Angelica Gutierrez-Barrera
,
Eric Hahnen
,
Jan Hauke
,
Alex Henderson
,
Julia Hentschel
,
Frans Hogervorst
,
Ellen Honisch
,
Evgeny Imyanitov
,
Claudine Isaacs
,
Louise Izatt
,
Angel Izquierdo
,
Anna Jakubowska
,
Paul James
,
Ramunas Janavicius
,
Uffe Birk Jensen
,
Esther John
,
Joseph Vijai
,
Katarzyna Kaczmarek
,
Beth Karlan
,
Karin Kast
,
Sung-Won Kim
,
Irene Konstantopoulou
,
Jacob Korach
,
Yael Laitman
,
Adriana Lasa
,
Christine Lasset
(1)
,
Conxi Lazaro
,
Annette Lee
,
Min Hyuk Lee
,
Jenny Lester
,
Fabienne Lesueur
(8)
,
Annelie Liljegren
,
Noralane Lindor
,
Michel Longy
(9)
,
Jennifer Loud
,
Karen Lu
,
Jan Lubinski
,
Eva Machackova
,
Siranoush Manoukian
,
Veronique Mari
(10)
,
Cristina Martínez-Bouzas
,
Zoltan Matrai
,
Noura Mebirouk
(8)
,
Hanne Meijers-Heijboer
,
Alfons Meindl
,
Arjen Mensenkamp
,
Ugnius Mickys
,
Austin Miller
,
Marco Montagna
,
Kirsten Moysich
,
Anna Marie Mulligan
,
Jacob Musinsky
,
Susan Neuhausen
,
Heli Nevanlinna
,
Joanne Ngeow
,
Huu Phuc Nguyen
,
Dieter Niederacher
,
Henriette Roed Nielsen
,
Finn Cilius Nielsen
,
Robert Nussbaum
,
Kenneth Offit
,
Anna Öfverholm
,
Kai-Ren Ong
,
Ana Osorio
,
Laura Papi
,
Janos Papp
,
Barbara Pasini
,
Inge Søkilde Pedersen
,
Ana Peixoto
,
Nina Peruga
,
Paolo Peterlongo
,
Esther Pohl
,
Nisha Pradhan
,
Karolina Prajzendanc
,
Fabienne Prieur
(11)
,
Pascal Pujol
(12, 13)
,
Paolo Radice
,
Susan Ramus
,
Johanna Rantala
,
Muhammad Usman Rashid
,
Kerstin Rhiem
,
Mark Robson
,
Gustavo Rodriguez
,
Mark Rogers
,
Vilius Rudaitis
,
Ane Schmidt
,
Rita Katharina Schmutzler
,
Leigha Senter
,
Payal Shah
,
Priyanka Sharma
,
Lucy Side
,
Jacques Simard
,
Christian Singer
,
Anne-Bine Skytte
,
Thomas Slavin
,
Katie Snape
,
Hagay Sobol
(14)
,
Melissa Southey
(14)
,
Linda Steele
,
Doris Steinemann
,
Grzegorz Sukiennicki
,
Christian Sutter
,
Csilla Szabo
,
Yen Tan
,
Manuel R Teixeira
,
Mary Beth Terry
,
Alex Teulé
,
Abigail Thomas
,
Darcy Thull
,
Marc Tischkowitz
,
Silvia Tognazzo
,
Amanda Ewart Toland
,
Sabine Topka
,
Alison Trainer
,
Nadine Tung
,
Christi van Asperen
,
Annemieke van Der Hout
,
Lizet van Der Kolk
,
Rob van Der Luijt
,
Mattias van Heetvelde
,
Liliana Varesco
,
Raymonda Varon-Mateeva
,
Ana Vega
,
Cynthia Villarreal-Garza
,
Anna von Wachenfeldt
,
Lisa Walker
,
Shan Wang-Gohrke
,
Barbara Wappenschmidt
,
Bernhard Weber
,
Drakoulis Yannoukakos
,
Sook-Yee Yoon
,
Cristina Zanzottera
,
Jamal Zidan
,
Kristin Zorn
,
Christina Hutten Selkirk
,
Peter Hulick
,
Georgia Chenevix-Trench
,
Amanda Spurdle
,
Antonis C. Antoniou
,
Katherine Nathanson
1
Centre Léon Bérard [Lyon]
2 Institut Curie [Paris]
3 CRLCC René Gauducheau
4 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
5 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
6 Centre Hospitalier Métropole Savoie [Chambéry]
7 CH Georges Renon Niort - Centre Hospitalier Georges Renon [Niort]
8 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
9 Plateforme de génétique moléculaire des cancers d'Aquitaine
10 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
11 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
12 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
13 UM - Université de Montpellier
14 IPC - Institut Paoli-Calmettes
2 Institut Curie [Paris]
3 CRLCC René Gauducheau
4 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
5 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
6 Centre Hospitalier Métropole Savoie [Chambéry]
7 CH Georges Renon Niort - Centre Hospitalier Georges Renon [Niort]
8 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
9 Plateforme de génétique moléculaire des cancers d'Aquitaine
10 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
11 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
12 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
13 UM - Université de Montpellier
14 IPC - Institut Paoli-Calmettes
Timothy Rebbeck
- Function : Author
- PersonId : 909919
Tara Friebel
- Function : Author
Eitan Friedman
- Function : Author
Ute Hamann
- Function : Author
Dezheng Huo
- Function : Author
Ava Kwong
- Function : Author
- PersonId : 922727
Edith Olah
- Function : Author
Olufunmilayo Olopade
- Function : Author
- PersonId : 920667
Angela Solano
- Function : Author
Soo-Hwang Teo
- Function : Author
- PersonId : 922722
Mads Thomassen
- Function : Author
Jeffrey Weitzel
- Function : Author
- PersonId : 920668
Tl Chan
- Function : Author
Fergus Couch
- Function : Author
- PersonId : 909921
David E. Goldgar
- Function : Author
Torben A. Kruse
- Function : Author
Edenir Inêz Palmero
- Function : Author
Sue Kyung Park
- Function : Author
Diana Torres
- Function : Author
Elizabeth Jansen van Rensburg
- Function : Author
- PersonId : 922726
Lesley Mcguffog
- Function : Author
- PersonId : 909942
Michael Parsons
- Function : Author
- PersonId : 797799
- ORCID : 0000-0003-3242-8477
Goska Leslie
- Function : Author
- PersonId : 791342
- ORCID : 0000-0001-5756-6222
Cora Aalfs
- Function : Author
- PersonId : 910047
Julio Abugattas
- Function : Author
Julian Adlard
- Function : Author
- PersonId : 920626
Simona Agata
- Function : Author
Kristiina Aittomäki
- Function : Author
Lesley Andrews
- Function : Author
Irene Andrulis
- Function : Author
- PersonId : 920702
Adalgeir Arason
- Function : Author
Norbert Arnold
- Function : Author
Banu Arun
- Function : Author
Ella Asseryanis
- Function : Author
Leo Auerbach
- Function : Author
Jacopo Azzollini
- Function : Author
- PersonId : 773228
- ORCID : 0000-0002-9364-9778
Judith Balmaña
- Function : Author
Monica Barile
- Function : Author
Rosa Barkardottir
- Function : Author
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Daniel Barrowdale
- Function : Author
- PersonId : 768869
- ORCID : 0000-0003-1661-3939
Javier Benitez
- Function : Author
Andreas Berger
- Function : Author
Raanan Berger
- Function : Author
Amie Blanco
- Function : Author
Kathleen Blazer
- Function : Author
Marinus Blok
- Function : Author
- PersonId : 907009
Bernardo Bonanni
- Function : Author
- PersonId : 920618
Angela Bradbury
- Function : Author
Carole Brewer
- Function : Author
- PersonId : 909882
Saundra Buys
- Function : Author
- PersonId : 909902
Trinidad Caldés
- Function : Author
- PersonId : 762555
- ORCID : 0000-0002-1038-5392
Almuth Caliebe
- Function : Author
Maria Adelaide Caligo
- Function : Author
- PersonId : 892831
Ian Campbell
- Function : Author
Sandrine Caputo
- Function : Author
- PersonId : 756410
- ORCID : 0000-0001-5338-9388
- IdRef : 111394759
Jocelyne Chiquette
- Function : Author
Wendy Chung
- Function : Author
- PersonId : 920701
Kathleen Claes
- Function : Author
- PersonId : 791343
- ORCID : 0000-0003-0841-7372
J Margriet Collée
- Function : Author
- PersonId : 922689
Jackie Cook
- Function : Author
- PersonId : 909879
Rosemarie Davidson
- Function : Author
- PersonId : 909877
Miguel de La Hoya
- Function : Author
Kim de Leeneer
- Function : Author
- PersonId : 907319
Orland Diez
- Function : Author
- PersonId : 871497
Yuan Chun Ding
- Function : Author
Nina Ditsch
- Function : Author
- PersonId : 922728
Susan Domchek
- Function : Author
- PersonId : 909917
Cecilia Dorfling
- Function : Author
Carolina Velazquez
- Function : Author
Bernd Dworniczak
- Function : Author
Jacqueline Eason
- Function : Author
- PersonId : 920630
Douglas F. Easton
- Function : Author
Ros Eeles
- Function : Author
- PersonId : 909874
Hans Ehrencrona
- Function : Author
- PersonId : 909911
Bent Ejlertsen
- Function : Author
Christoph Engel
- Function : Author
Stefanie Engert
- Function : Author
D Gareth Evans
- Function : Author
- PersonId : 889745
Lídia Feliubadaló
- Function : Author
Lenka Foretova
- Function : Author
Jeffrey Fowler
- Function : Author
Debra Frost
- Function : Author
- PersonId : 909872
Henrique Galvão
- Function : Author
Patricia Ganz
- Function : Author
Judy Garber
- Function : Author
Andrea Gehrig
- Function : Author
- PersonId : 922730
Anne-Marie Gerdes
- Function : Author
- PersonId : 920687
Giuseppe Giannini
- Function : Author
Sophie Giraud
- Function : Author
- PersonId : 1359982
- ORCID : 0000-0003-1243-3084
Gord Glendon
- Function : Author
- PersonId : 920685
Andrew Godwin
- Function : Author
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Mark Greene
- Function : Author
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- ORCID : 0000-0003-1852-9239
Jacek Gronwald
- Function : Author
Angelica Gutierrez-Barrera
- Function : Author
Eric Hahnen
- Function : Author
Jan Hauke
- Function : Author
Alex Henderson
- Function : Author
Julia Hentschel
- Function : Author
Frans Hogervorst
- Function : Author
- PersonId : 909029
Ellen Honisch
- Function : Author
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Evgeny Imyanitov
- Function : Author
- PersonId : 909933
Claudine Isaacs
- Function : Author
- PersonId : 908788
Louise Izatt
- Function : Author
- PersonId : 909875
Angel Izquierdo
- Function : Author
Anna Jakubowska
- Function : Author
- PersonId : 906670
Paul James
- Function : Author
- PersonId : 791346
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Ramunas Janavicius
- Function : Author
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Uffe Birk Jensen
- Function : Author
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Esther John
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Joseph Vijai
- Function : Author
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Katarzyna Kaczmarek
- Function : Author
Beth Karlan
- Function : Author
- PersonId : 920697
Karin Kast
- Function : Author
- PersonId : 922731
Sung-Won Kim
- Function : Author
Irene Konstantopoulou
- Function : Author
Jacob Korach
- Function : Author
Yael Laitman
- Function : Author
Adriana Lasa
- Function : Author
Conxi Lazaro
- Function : Author
- PersonId : 882455
Annette Lee
- Function : Author
Min Hyuk Lee
- Function : Author
Jenny Lester
- Function : Author
Fabienne Lesueur
- Function : Author
- PersonId : 918641
Annelie Liljegren
- Function : Author
- PersonId : 910063
Noralane Lindor
- Function : Author
- PersonId : 920672
Michel Longy
- Function : Author
- PersonId : 955030
Jennifer Loud
- Function : Author
- PersonId : 922735
Karen Lu
- Function : Author
Jan Lubinski
- Function : Author
- PersonId : 869805
Eva Machackova
- Function : Author
Siranoush Manoukian
- Function : Author
Cristina Martínez-Bouzas
- Function : Author
Zoltan Matrai
- Function : Author
Hanne Meijers-Heijboer
- Function : Author
Alfons Meindl
- Function : Author
Arjen Mensenkamp
- Function : Author
Ugnius Mickys
- Function : Author
Austin Miller
- Function : Author
- PersonId : 798123
- ORCID : 0000-0001-9739-8462
Marco Montagna
- Function : Author
Kirsten Moysich
- Function : Author
Anna Marie Mulligan
- Function : Author
Jacob Musinsky
- Function : Author
Susan Neuhausen
- Function : Author
- PersonId : 920693
Heli Nevanlinna
- Function : Author
- PersonId : 908074
Joanne Ngeow
- Function : Author
Huu Phuc Nguyen
- Function : Author
Dieter Niederacher
- Function : Author
Henriette Roed Nielsen
- Function : Author
Finn Cilius Nielsen
- Function : Author
Robert Nussbaum
- Function : Author
- PersonId : 791348
- ORCID : 0000-0003-3445-8880
Kenneth Offit
- Function : Author
Anna Öfverholm
- Function : Author
Kai-Ren Ong
- Function : Author
- PersonId : 909878
Ana Osorio
- Function : Author
Laura Papi
- Function : Author
Janos Papp
- Function : Author
Barbara Pasini
- Function : Author
Inge Søkilde Pedersen
- Function : Author
Ana Peixoto
- Function : Author
Nina Peruga
- Function : Author
Paolo Peterlongo
- Function : Author
- PersonId : 762723
- ORCID : 0000-0001-6951-6855
Esther Pohl
- Function : Author
Nisha Pradhan
- Function : Author
Karolina Prajzendanc
- Function : Author
Fabienne Prieur
- Function : Author
- PersonId : 922702
Pascal Pujol
- Function : Author
- PersonId : 840596
Paolo Radice
- Function : Author
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Susan Ramus
- Function : Author
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Johanna Rantala
- Function : Author
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Muhammad Usman Rashid
- Function : Author
Kerstin Rhiem
- Function : Author
- PersonId : 920635
Mark Robson
- Function : Author
- PersonId : 795764
- ORCID : 0000-0002-3109-1692
Gustavo Rodriguez
- Function : Author
Mark Rogers
- Function : Author
- PersonId : 922696
Vilius Rudaitis
- Function : Author
Ane Schmidt
- Function : Author
Rita Katharina Schmutzler
- Function : Author
Leigha Senter
- Function : Author
Payal Shah
- Function : Author
Priyanka Sharma
- Function : Author
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- ORCID : 0000-0003-3890-3590
Lucy Side
- Function : Author
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Jacques Simard
- Function : Author
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- ORCID : 0000-0001-6906-3390
Christian Singer
- Function : Author
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Anne-Bine Skytte
- Function : Author
- PersonId : 920689
Thomas Slavin
- Function : Author
Katie Snape
- Function : Author
Linda Steele
- Function : Author
Doris Steinemann
- Function : Author
Grzegorz Sukiennicki
- Function : Author
Christian Sutter
- Function : Author
Csilla Szabo
- Function : Author
Yen Tan
- Function : Author
Manuel R Teixeira
- Function : Author
Mary Beth Terry
- Function : Author
Alex Teulé
- Function : Author
- PersonId : 922717
Abigail Thomas
- Function : Author
Darcy Thull
- Function : Author
Marc Tischkowitz
- Function : Author
Silvia Tognazzo
- Function : Author
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Amanda Ewart Toland
- Function : Author
Sabine Topka
- Function : Author
Alison Trainer
- Function : Author
Nadine Tung
- Function : Author
Christi van Asperen
- Function : Author
- PersonId : 910048
Annemieke van Der Hout
- Function : Author
Lizet van Der Kolk
- Function : Author
Rob van Der Luijt
- Function : Author
- PersonId : 920624
Mattias van Heetvelde
- Function : Author
Liliana Varesco
- Function : Author
Raymonda Varon-Mateeva
- Function : Author
- PersonId : 920641
Ana Vega
- Function : Author
- PersonId : 887296
Cynthia Villarreal-Garza
- Function : Author
Anna von Wachenfeldt
- Function : Author
Lisa Walker
- Function : Author
Shan Wang-Gohrke
- Function : Author
Barbara Wappenschmidt
- Function : Author
Bernhard Weber
- Function : Author
Drakoulis Yannoukakos
- Function : Author
- PersonId : 764694
- ORCID : 0000-0001-7509-3510
- IdRef : 111519055
Sook-Yee Yoon
- Function : Author
Cristina Zanzottera
- Function : Author
Jamal Zidan
- Function : Author
Kristin Zorn
- Function : Author
- PersonId : 798124
- ORCID : 0000-0003-2143-8979
Christina Hutten Selkirk
- Function : Author
Peter Hulick
- Function : Author
- PersonId : 791345
- ORCID : 0000-0001-8397-4078
Georgia Chenevix-Trench
- Function : Author
Amanda Spurdle
- Function : Author
Antonis C. Antoniou
- Function : Author
Katherine Nathanson
- Function : Author
- PersonId : 909918
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.
Domains
Human geneticsOrigin | Files produced by the author(s) |
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