Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach

Sandrine M. Caputo; Lisa Golmard; Mélanie Léone; Francesca Damiola; Marine Guillaud-Bataille; Françoise Revillion; Etienne Rouleau; Nicolas Derive; Adrien Buisson; Noémie Basset; Mathias Schwartz; Paul Vilquin; Celine Garrec; Maud Privat; Mathilde Gay-Bellile; Caroline Abadie; Khadija Abidallah; Fabrice Airaud; Anne-Sophie Allary; Emmanuelle Barouk-Simonet; Muriel Belotti; Charlotte Benigni; Patrick R. Benusiglio; Christelle Berthemin; Pascaline Berthet; Ophelie Bertrand; Stéphane Bézieau; Marie Bidart; Yves-Jean Bignon; Anne-Marie Birot; Maud Blanluet; Amelie Bloucard; Johny Bombled; Valerie Bonadona; Françoise Bonnet; Marie-Noëlle Bonnet-Dupeyron; Manon Boulaire; Flavie Boulouard; Ahmed Bouras; Violaine Bourdon; Afane Brahimi; Fanny Brayotel; Brigitte Bressac de Paillerets; Noémie Bronnec; Virginie Bubien; Bruno Buecher; Odile Cabaret; Jennifer Carriere; Jean Chiesa; Stephanie Chieze-Valéro; Camille Cohen; Odile Cohen-Haguenauer; Chrystelle Colas; Marie-Agnès Collonge-Rame; Anne-Laure Conoy; Florence Coulet; Isabelle Coupier; Louise Crivelli; Véronica Cusin; Antoine De Pauw; Catherine Dehainault; Hélène Delhomelle; Capucine Delnatte; Sophie Demontety; Philippe Denizeau; Pierre Devulder; Helene Dreyfus; Catherine Dubois d’Enghein; Anaïs Dupré; Anne Durlach; Sophie Dussart; Anne Fajac; Samira Fekairi; Sandra Fert-Ferrer; Alice Fiévet; Robin Fouillet; Emmanuelle Mouret-Fourme; Marion Gauthier-Villars; Paul Gesta; Sophie Giraud; Laurence Gladieff; Veronica Goldbarg; Vincent Goussot; Virginie Guibert; Erell Guillerm; Christophe Guy; Agnès Hardouin; Céline Heude; Claude Houdayer; Olivier Ingster; Caroline Jacquot-Sawka; Natalie Jones; Sophie Krieger; Sofiane Lacoste; Hakima Lallaoui; Helene Larbre; Anthony Laugé; Gabrielle Le Guyadec; Marine Le Mentec; Caroline Lecerf; Jessica Le Gall; Bérengère Legendre; Clémentine Legrand; Angélina Legros; Sophie Lejeune; Rosette Lidereau; Norbert Lignon; Jean-Marc Limacher; Doriane Livon; Sarab Lizard; Michel Longy; Alain Lortholary; Pierre Macquere; Audrey Mailliez; Sarah Malsa; Henri Margot; Véronique Mari; Christine Maugard; Cindy Meira; Julie Menjard; Diane Molière; Virginie Moncoutier; Jessica Moretta-Serra; Etienne Muller; Zoe Nevière; Thien-vu Nguyen Minh Tuan; Tetsuro Noguchi; Catherine Noguès; Florine Oca; Cornel Popovici; Fabienne Prieur; Sabine Raad; Jean-Marc Rey; Agathe Ricou; Lucie Salle; Claire Saule; Nicolas Sevenet; Fatoumata Simaga; Hagay Sobol; Voreak Suybeng; Isabelle Tennevet; Henrique Tenreiro; Julie Tinat; Christine Toulas; Isabelle Turbiez; Nancy Uhrhammer; Pierre Vande Perre; Dominique Vaur; Laurence Venat; Nicolas Viellard; Marie-Charlotte Villy; Mathilde Warcoin; Alice Yvard; Helene Zattara; Olivier Caron; Christine Lasset; Audrey Remenieras; Nadia Boutry-Kryza; Laurent Castéra; Dominique Stoppa-Lyonnet

doi:10.1016/j.ajhg.2021.09.003

Retour

Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach

Article de revue

Avec comité de lecture

Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach

Sandrine M. Caputo, Lisa Golmard, Mélanie Léone, Francesca Damiola, Marine Guillaud-Bataille, Françoise Revillion, Etienne Rouleau, Nicolas Derive, Adrien Buisson, Noémie Basset, …

American journal of human genetics, Vol.108(10), pp.1907-1923

07/10/2021

DOI: https://doi.org/10.1016/j.ajhg.2021.09.003

PMID: 34597585

Résumé

BRCA1

BRCA2

classification

clinical

cosegregation data

multifactorial model

variant of uncertain significance

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs. The classification method was a multifactorial model combining different associations between VUSs and cancer, including cosegregation data. At this time, among the 653 variants selected, 101 (15%) distinct variants shared by 1,624 families were classified as pathogenic/likely pathogenic or benign/likely benign by the COVAR study. Sixty-six of the 101 (65%) variants classified by COVAR would have remained VUSs without cosegregation data. Of note, among the 34 variants classified as pathogenic by COVAR, 16 remained VUSs or likely pathogenic when following the ACMG/AMP variant classification guidelines. Although the initiation and organization of cosegregation analyses require a considerable effort, the growing number of available genetic tests results in an increasing number of families sharing a particular variant, and thereby increases the power of such analyses. Here we demonstrate that variant cosegregation analyses are a powerful tool for the classification of variants in the BRCA1/2 breast-ovarian cancer predisposition genes.

Indicateurs

1 Consultations de la notice

See more details

Détails

Titre: Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach
Créateurs - sans rôle: Sandrine M. Caputo - Department of Genetics, Institut Curie, Paris 75005, France
Lisa Golmard - Institut Curie
Mélanie Léone - Service de Génétique, plate-forme mixte des cancers fréquents, Hospices Civils de Lyon, Bron 69229, France
Francesca Damiola - Centre Léon Bérard
Marine Guillaud-Bataille - Service de Génétique des Tumeurs, Gustave Roussy, Villejuif 94806, France
Françoise Revillion - Centre Oscar Lambret
Etienne Rouleau - Service de Génétique des Tumeurs, Gustave Roussy, Villejuif 94806, France
Nicolas Derive - Department of Genetics, Institut Curie, Paris 75005, France
Adrien Buisson - Service de Génétique, plate-forme mixte des cancers fréquents, Hospices Civils de Lyon, Bron 69229, France
Noémie Basset - Département de génétique, AP-HP, Sorbonne université-Site Pitié-Salpêtrière, Paris 75013, France
Mathias Schwartz - Department of Genetics, Institut Curie, Paris 75005, France
Paul Vilquin - Département Pathologie et Oncobiologie, CHU Montpellier, Montpellier 34070, France
Celine Garrec - Laboratoire de Génétique Moléculaire, Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) de Nantes, Nantes 44093, France
Maud Privat - Département d’Oncogénétique, Centre Jean Perrin, Clermont-Ferrand 63000, France
Mathilde Gay-Bellile - Département d’Oncogénétique, Centre Jean Perrin, Clermont-Ferrand 63000, France
Caroline Abadie - Institut de Cancérologie de l'Ouest
Khadija Abidallah - Institut Curie
Fabrice Airaud - Université de Nantes
Anne-Sophie Allary - Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli Calmettes, Marseille 13273, France
Emmanuelle Barouk-Simonet - Institut Bergonié
Muriel Belotti - Department of Genetics, Institut Curie, Paris 75005, France
Charlotte Benigni - Hôpital d’Enfants, CHRU Nancy Hopitaux de Brabois, Vandoeuvre les Nancy 54500, France
Patrick R. Benusiglio - UF d’Oncogénétique, GH Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris 75013, France
Christelle Berthemin - Department of Genetics, Institut Curie, Paris 75005, France
Pascaline Berthet - Oncogenetic, Department of Biopathology, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Ophelie Bertrand - Department of Genetics, Institut Curie, Saint-Cloud 92210, France
Stéphane Bézieau - Laboratoire de Génétique Moléculaire, Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) de Nantes, Nantes 44093, France
Marie Bidart - Laboratoire de Génétique Moléculaire: Maladies Héréditaires et Oncologie, CHU Grenoble Alpes, Grenoble 38700, France
Yves-Jean Bignon - Department of Oncogenetics, Centre Jean Perrin, UMR INSERM 1240, Université Clermont Auvergne, Clermont-Ferrand Cedex 63011, France
Anne-Marie Birot - Service de Génétique, Hôpital Européen Georges Pompidou, Paris 75015, France
Maud Blanluet - Institut Curie
Amelie Bloucard - Department of Genetics, Institut Curie, Paris 75005, France
Johny Bombled - Service de Génétique des Tumeurs, Gustave Roussy, Villejuif 94806, France
Valerie Bonadona - Centre Léon Bérard
Françoise Bonnet - Institut Bergonié
Marie-Noëlle Bonnet-Dupeyron - Consultations de Génétique, Centre Hospitalier de Valence, Valence 26953, France
Manon Boulaire - Department of Genetics, Centre Oscar Lambret, Lille 59000, France
Flavie Boulouard - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Ahmed Bouras - Service de Génétique, plate-forme mixte des cancers fréquents, Hospices Civils de Lyon, Bron 69229, France
Violaine Bourdon - Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli Calmettes, Marseille 13273, France
Afane Brahimi - Department of Genetics, CHU Lille, Lille 59000, France
Fanny Brayotel - Oncogenetics Laboratory, Institut Godinot, Reims 51726, France
Brigitte Bressac de Paillerets - Service de Génétique des Tumeurs, Gustave Roussy, Villejuif 94806, France
Noémie Bronnec - Génétique Médicale, CHU Bordeaux, Bordeaux 33076, France
Virginie Bubien - Institut Bergonié
Bruno Buecher - Institut Curie
Odile Cabaret - Service de Génétique des Tumeurs, Gustave Roussy, Villejuif 94806, France
Jennifer Carriere - Department of Genetics, Institut Curie, Paris 75005, France
Jean Chiesa - Department of Genetics, Centre Hospitalier Régional Universitaire, Nimes 30029, France
Stephanie Chieze-Valéro - Service Oncogénétique Régional Poitou-Charentes, CH Georges Renon, Niort 79000, France
Camille Cohen - Service de Génétique, CHI de Poissy-Saint Germain En Laye, Poissy 78300, France
Odile Cohen-Haguenauer - Service de Génétique, CHI de Poissy-Saint Germain En Laye, Poissy 78300, France
Chrystelle Colas - Institut Curie
Marie-Agnès Collonge-Rame - Oncobiologie Génétique Bioinformatique, CHRU Besançon, Besançon 25030, France
Anne-Laure Conoy - Department of Genetics, Centre Oscar Lambret, Lille 59000, France
Florence Coulet - Assistance Publique – Hôpitaux de Paris
Isabelle Coupier - Département Pathologie et Oncobiologie, CHU Montpellier, Montpellier 34070, France
Louise Crivelli - Centre Eugène Marquis
Véronica Cusin - Département de génétique, AP-HP, Sorbonne université-Site Pitié-Salpêtrière, Paris 75013, France
Antoine De Pauw - Institut Curie
Catherine Dehainault - Department of Genetics, Institut Curie, Paris 75005, France
Hélène Delhomelle - Department of Genetics, Institut Curie, Saint-Cloud 92210, France
Capucine Delnatte - Université de Nantes
Sophie Demontety - Department of Genetics, Institut Curie, Paris 75005, France
Philippe Denizeau - Université Rennes 1
Pierre Devulder - Oncogenetic, Department of Biopathology, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Helene Dreyfus - Institut Sainte Catherine
Catherine Dubois d’Enghein - Department of Genetics, Institut Curie, Paris 75005, France
Anaïs Dupré - Unité d’Oncogénétique, Institut Bergonié, Bordeaux 33076, France
Anne Durlach - Consultation oncogénétique, CHU Reims, Reims 51092, France
Sophie Dussart - Centre Léon Bérard
Anne Fajac - Assistance Publique – Hôpitaux de Paris
Samira Fekairi - Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli Calmettes, Marseille 13273, France
Sandra Fert-Ferrer - UF Consultation de génétique, Centre Hospitalier Métropole Savoie, Chambéry 73011, France
Alice Fiévet - Service de Génétique des Tumeurs, Gustave Roussy, Villejuif 94806, France
Robin Fouillet - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Emmanuelle Mouret-Fourme - Institut Curie
Marion Gauthier-Villars - Department of Genetics, Institut Curie, Paris 75005, France
Paul Gesta - Service Oncogénétique Régional Poitou-Charentes, CH Georges Renon, Niort 79000, France
Sophie Giraud - Hospices Civils de Lyon
Laurence Gladieff - Institut Claudius Regaud
Veronica Goldbarg - Gustave Roussy, Département de médecine oncologique, Villejuif 94805, France
Vincent Goussot - Centre Georges François Leclerc
Virginie Guibert - Laboratoire de Génétique Moléculaire, Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) de Nantes, Nantes 44093, France
Erell Guillerm - Département de génétique, AP-HP, Sorbonne université-Site Pitié-Salpêtrière, Paris 75013, France
Christophe Guy - Department of Genetics, Institut Curie, Paris 75005, France
Agnès Hardouin - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Céline Heude - Oncogenetic, Department of Biopathology, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Claude Houdayer - Institut Curie
Olivier Ingster - Centre Hospitalier Universitaire d'Angers
Caroline Jacquot-Sawka - Centre de Génétique, CHU de Dijon (hopital François Mitterand) and CLCC de Dijon (Centre Georges François Leclerc), Dijon 21000, France
Natalie Jones - Institut Bergonié
Sophie Krieger - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Sofiane Lacoste - Department of Genetics, Institut Curie, Paris 75005, France
Hakima Lallaoui - CH La rochelle, La Rochelle 17000, France
Helene Larbre - Oncogenetics Laboratory, Institut Godinot, Reims 51726, France
Anthony Laugé - Institut Curie
Gabrielle Le Guyadec - Laboratoire de Génétique Moléculaire: Maladies Héréditaires et Oncologie, CHU Grenoble Alpes, Grenoble 38700, France
Marine Le Mentec - Department of Genetics, Institut Curie, Paris 75005, France
Caroline Lecerf - Department of Genetics, Institut Curie, Paris 75005, France
Jessica Le Gall - Department of Genetics, Institut Curie, Paris 75005, France
Bérengère Legendre - Department of Genetics, Centre Oscar Lambret, Lille 59000, France
Clémentine Legrand - Service de Génétique, CHU Grenoble Alpes, Grenoble 38700, France
Angélina Legros - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Sophie Lejeune - Department of Genetics, CHU Lille, Lille 59000, France
Rosette Lidereau - Institut Curie
Norbert Lignon - Oncogenetics Department, Institut Claudius Regaud, Toulouse 31059, France
Jean-Marc Limacher - Génétique Oncologique Clinique, Hospices Civils de Colmar, Colmar 68000, France
Doriane Livon - Department of Clinical Cancer Genetics, Institut Paoli-Calmettes, Marseille 13273, France
Sarab Lizard - Department of Genetics, CHRU Nancy Hopitaux de Brabois, Vandoeuvre les Nancy 54500, France
Michel Longy - Institut Bergonié
Alain Lortholary - Department of Genetics, Hôpital Privé du Confluent, Nantes 44202, France
Pierre Macquere - Unité d’Oncogénétique, Institut Bergonié, Bordeaux 33076, France
Audrey Mailliez - Centre Oscar Lambret
Sarah Malsa - Department of Genetics, CHU de Martinique, Fort de France 97200, Martinique
Henri Margot - Institut Bergonié
Véronique Mari - Centre Antoine Lacassagne
Christine Maugard - Génétique Oncologique Moléculaire, Hôpital de Hautepierre, Strasbourg 67000, France
Cindy Meira - Department of Genetics, Centre Oscar Lambret, Lille 59000, France
Julie Menjard - Department of Genetics, CHU Brest, Brest 29600, France
Diane Molière - Service de Génétique, Hôpital Européen Georges Pompidou, Paris 75015, France
Virginie Moncoutier - Department of Genetics, Institut Curie, Paris 75005, France
Jessica Moretta-Serra - Department of Clinical Cancer Genetics, Institut Paoli-Calmettes, Marseille 13273, France
Etienne Muller - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Zoe Nevière - Oncogenetic, Department of Biopathology, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Thien-vu Nguyen Minh Tuan - Department of Genetics, Institut Curie, Paris 75005, France
Tetsuro Noguchi - Department of Cancer Biology, Laboratory of Molecular Oncogenetics, Institut Paoli Calmettes, Marseille 13273, France
Catherine Noguès - Department of Clinical Cancer Genetics, Institut Paoli-Calmettes, Marseille 13273, France
Florine Oca - Department of Genetics, Centre Oscar Lambret, Lille 59000, France
Cornel Popovici - Institut Paoli-Calmettes
Fabienne Prieur - Service de Génétique, CHU St Etienne, Saint Etienne 42055, France
Sabine Raad - Unité d’Oncogénétique, Institut Bergonié, Bordeaux 33076, France
Jean-Marc Rey - Département Pathologie et Oncobiologie, CHU Montpellier, Montpellier 34070, France
Agathe Ricou - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Lucie Salle - Service Oncogénétique Régional Poitou-Charentes, CH Georges Renon, Niort 79000, France
Claire Saule - Institut Curie
Nicolas Sevenet - Institut Bergonié
Fatoumata Simaga - Institut Curie
Hagay Sobol - Institut Paoli-Calmettes
Voreak Suybeng - Department of Genetics, Institut Curie, Paris 75005, France
Isabelle Tennevet - Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen 76031, France
Henrique Tenreiro - Department of Genetics, Institut Curie, Paris 75005, France
Julie Tinat - Génétique Médicale, CHU Bordeaux, Bordeaux 33076, France
Christine Toulas - Institut Claudius Regaud
Isabelle Turbiez - Clinical research direction, Institut Curie, Paris 75005, France
Nancy Uhrhammer - Centre Jean Perrin
Pierre Vande Perre - Institut Claudius Regaud
Dominique Vaur - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Laurence Venat - Department of oncology, CHU Dupuytren, Limoges 87042, France
Nicolas Viellard - Department of Genetics, Institut Curie, Paris 75005, France
Marie-Charlotte Villy - Department of Genetics, Institut Curie, Paris 75005, France
Mathilde Warcoin - Department of Genetics, Institut Curie, Paris 75005, France
Alice Yvard - Department of Genetics, Hôpital Privé du Confluent, Nantes 44202, France
Helene Zattara - Centre Oscar Lambret
Olivier Caron - Gustave Roussy, Département de médecine oncologique, Villejuif 94805, France
Christine Lasset - Centre Léon Bérard
Audrey Remenieras - Institut Paoli-Calmettes
Nadia Boutry-Kryza - Hospices Civils de Lyon
Laurent Castéra - Laboratory of Cancer Biology and Genetics, Comprehensive Cancer Center François Baclesse, Caen 14076, France
Dominique Stoppa-Lyonnet - Institut Curie
Détails de publication: American journal of human genetics, Vol.108(10), pp.1907-1923
Éditeur: Elsevier Inc
Nombre de pages: 17
Identifiants: 99162951609311
Unité académique: Institut des Biomolécules Max Mousseron - IBMM
Langue: English
Type de ressource: Journal article