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Record W2789006266 · doi:10.1002/humu.23406

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

2018· article· en· W2789006266 on OpenAlexafffund
Timothy R. Rebbeck, Tara M. Friebel, Eitan Friedman, Ute Hamann, Dezheng Huo, Ava Kwong, Edith Oláh, Olufunmilayo I. Olopade, Ángela R. 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 Torres, Elizabeth J. 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 Arun, Ella Asseryanis, Leo Auerbach, Jacopo Azzollini, Judith Balmañà, Monica Barile, Rósa B. Barkardóttir, Daniel Barrowdale, Javier Benı́tez, Andreas Berger, Raanan Berger, Amie Blanco, Kathleen R. Blazer, Marinus J. Blok, Valérie Bonadona, Bernardo Bonanni, Angela R. Bradbury, Carole Brewer, Bruno Buecher, Saundra S. Buys, Trinidad Caldés, Almuth Caliebe, Maria A. Caligo, Ian Campbell, Sandrine M. Caputo, Jocelyne Chiquette, Wendy K. Chung, Kathleen Claes, J. Margriet Collée, Jackie Cook, Rosemarie Davidson, Miguel de la Hoya, Kim De Leeneer, Antoine De Pauw, Capucine Delnatte, Orland Dı́ez, Yuan Chun Ding, Nina Ditsch, Susan M. Domchek, Cecilia M. Dorfling, Carolina Velázquez, Bernd Dworniczak, Jacqueline Eason, Douglas F. Easton, Rosalind A. Eeles, Hans Ehrencrona, Bent Ejlertsen, Christoph Engel, Stefanie Engert, D. Gareth Evans, Laurence Faivre, Lídia Feliubadaló, Sandra Fert Ferrer, Lenka Foretová, Jeffrey M. Fowler, Debra Frost, Henrique C.R. Galvão, Patricia A. Ganz, Judy E. Garber, Marion Gauthier‐Villars, Andrea Gehrig, 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, Alex Henderson, Julia Hentschel, Frans B. L. Hogervorst, Ellen Honisch, Evgeny N. Imyanitov, Claudine Isaacs, Louise Izatt, Á. Izquierdo, Anna Jakubowska, Paul A. 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 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 Nevanlinna, Joanne Ngeow, Huu Phuc Nguyen, Dieter Niederacher, Henriette Roed Nielsen, Finn C. Nielsen, Robert L. 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 K. Schmutzler, Leigha Senter, Payal D. Shah, Priyanka Sharma, Lucy Side, Jacques Simard, Christian F. Singer, Anne‐Bine Skytte, Thomas P. Slavin, Katie Snape, Hagay Sobol, Melissa C. Southey, Linda Steele, Doris Steinemann, Grzegorz Sukiennicki, Christian Sutter, Csilla I. Szabo, Yen Y. Tan, Manuel R. Teixeira, Mary Beth Terry, Àlex Teulé, Abigail Thomas, Darcy L. Thull, Marc 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 Vega, Cynthia 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

Bibliographic record

VenueHuman Mutation · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsMcGill UniversityUniversité LavalLunenfeld-Tanenbaum Research InstituteMount Sinai HospitalCentre hospitalier universitaire de QuébecHôpital du Saint-SacrementUniversity of Toronto
FundersJonsson Comprehensive Cancer CenterNational Center for Advancing Translational SciencesInstituto de Salud Carlos IIICanadian Institutes of Health Researchlékařská fakulta Univerzity KarlovyNational Institutes of HealthCentro de Investigación Biomédica en Red de CáncerFox Chase Cancer CenterMinistero dello Sviluppo EconomicoMedical Research CouncilUppsala UniversitetHospices Civils de LyonRadboud Universitair Medisch CentrumSahlgrenska UniversitetssjukhusetInstitut National Du CancerLeids Universitair Medisch CentrumAssociazione Italiana per la Ricerca sul CancroFinanciadora de Estudos e ProjetosKWF KankerbestrijdingLietuvos Mokslo TarybaLinköpings UniversitetHungarian Scientific Research FundLunds UniversitetPontificia Universidad JaverianaNederlandse Organisatie voor Wetenschappelijk OnderzoekMinistero della SaluteInstitut Català de la SalutInstitut Gustave-RoussyUniversity of PennsylvaniaConsejo Nacional de Investigaciones Científicas y TécnicasNorway GrantsGeneralitat de CatalunyaErasmus Medisch CentrumVrije Universiteit AmsterdamFundación Mutua MadrileñaMinistère du Développement Économique, de l’Innovation et de l’ExportationRadboud UniversiteitNational Medical Research CouncilMaastricht Universitair Medisch CentrumUniversiteit LeidenCancer Association of South AfricaMinisterstvo Školství, Mládeže a TělovýchovyNational Breast Cancer FoundationNemzeti Kutatási Fejlesztési és Innovációs HivatalNational Institute for Health and Care ResearchCanadian Breast Cancer Research AllianceCentre Léon BérardGovernment of CanadaNational Cancer InstituteLiga Portuguesa Contra o CancroHospital de Câncer de BarretosFundação de Amparo à Pesquisa do Estado de São PauloEuropean CommissionNorthShore University HealthSystemCancer Research UKMemorial Sloan-Kettering Cancer CenterFondation du cancer du sein du QuébecWellcome TrustDavid F. and Margaret T. Grohne Family FoundationMcGill UniversityBreast Cancer Research FoundationUniverzita Karlova v PrazeUnicancerDeutsches KrebsforschungszentrumCancer Center, University of KansasCancerfondenIstituto Oncologico VenetoUmeå UniversitetRoyal Marsden NHS Foundation TrustDeutsche KrebshilfeLee FoundationGenome CanadaRijksuniversiteit GroningenUniversity of California, San FranciscoCreighton UniversityNRG OncologyDr. Ralph and Marian Falk Medical Research TrustKansas Bioscience AuthorityNational Health and Medical Research CouncilJewish General HospitalFisher Center for Alzheimer's Research FoundationFundación CellexEuropean Regional Development FundJess and Mildred Fisher Center for Familial Cancer ResearchIstituto Pasteur-Fondazione Cenci BolognettiCancer AustraliaLandspítali HáskólasjúkrahúsMinisterio de Economía y CompetitividadOvarian Cancer Research FundUniversiteit MaastrichtEuropean Social FundUniversity of ChicagoSusan G. Komen for the CureGeorgetown UniversityFonds Wetenschappelijk OnderzoekAmerican Cancer Society
KeywordsFounder effectGeneticsBiologyGenotypingMutationGermline mutationAllele frequencyPopulationGermlineEvolutionary biologyAlleleGenotypeHaplotypeGeneDemography

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.298
Teacher spread0.281 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations314
Published2018
Admission routes2
Has abstractyes

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