The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

Marie Eliade; Jeremy Skrzypski; Amandine Baurand; Caroline Jacquot; Geoffrey Bertolone; Catherine Loustalot; Charles Coutant; France Guy; Pierre Fumoleau; Yannis Duffourd; Laurent Arnould; Alexandra Delignette; Marie-Martine Padéano; Côme Lepage; Géraldine Raichon-Patru; Axelle Boudrant; Marie-Christine Bône-Lépinoy; Anne-Laure Villing; Aurélie Charpin; Karine Peignaux; Sandy Chevrier; François Vegran; François Ghiringhelli; Romain Boidot; Nicolas Sevenet; Sarab Lizard; Laurence Faivre

doi:10.18632/oncotarget.12699

Article dans une revue

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

Marie Eliade ¹ Jeremy Skrzypski Amandine Baurand ¹ Caroline Jacquot Geoffrey Bertolone Catherine Loustalot ² Charles Coutant ^{3, 4} France Guy ⁵ Pierre Fumoleau ⁶ Yannis Duffourd ^{3, 7} Laurent Arnould ^{2, 8, 9, 10} Alexandra Delignette ^{11, 7, 12} Marie-Martine Padéano ^{2, 8, 10, 12} Côme Lepage ^{10, 13} Géraldine Raichon-Patru ¹⁴ Axelle Boudrant ¹⁵ Marie-Christine Bône-Lépinoy ^{11, 4} Anne-Laure Villing Aurélie Charpin ^{6, 7} Karine Peignaux ¹³ Sandy Chevrier ¹⁶ François Vegran ⁴ François Ghiringhelli ⁴ Romain Boidot ⁴ Nicolas Sevenet ³ Sarab Lizard ¹² Laurence Faivre ^{1, 17, *}

* Auteur correspondant

1 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)

2 Centre Hospitalier d'Auxerre

3 Institut Bergonié [Bordeaux]

4 Plateforme de transfert en biologie cancérologique [Dijon]

CEP - Centre d'épidémiologie des populations, UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]

5 Imagerie Medicale Dijon Tour Elithis

6 Service de radiothérapie [Centre Georges-François Leclerc]

7 Centre Hospitalier Chalon-sur-Saône William Morey

8 Département d'oncologie médicale [Centre Georges-François Leclerc]

9 Orphanomix

10 Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon)

11 Service de radiologie [Centre Georges-François Leclerc]

12 Département de Biologie et pathologie des tumeurs [Centre Georges-François Leclerc]

13 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]

14 Service d'oncologie et hépatologie [Centre Hospitalier de Mâcon : les Chanaux]

15 Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey]

16 Clinique Drévon

17 Service d'oncogénétique [Centre georges-François Leclerc]

Abstract : Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2 testing. Next generation sequencing and the recent discovery of new genes involved in HBOC now permit the transfer of genomic capture targeting multiple candidate genes from research to clinical use. However, the implications for the management of patients and their families have not been extensively studied, in particular since some of these genes are not well-established cancer predisposing genes. We studied 583 consecutive patients from Burgundy (France) fulfilling the criteria for BRCA testing using a next generation sequencing 25-genes panel including 20 well-established high-risk cancer genes as well as more recently identified predisposing HBOC cancer. A pathogenic BRCA1/2 mutation was found in 51 patients (9%). Besides, we found 37 pathogenic or likely pathogenic mutations in 10 different high to low-risk genes in 34 patients (6%). The most frequently mutated genes were CHEK2 (n = 12; 2%), ATM (n = 9; 1.5%), and PALB2 (n = 4; 0.6%). Three patients had a mutation in two different predisposing genes. The analysis of clinical actionability conducted in mutation-positive individuals revealed that additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone had been recommended in 69% of cases. In conclusion, multigene panel testing is a powerful tool to identifying high to low-risk HBOC susceptibility genes. The penetrance and spectrum of cancers with these other genes are sometimes undefined, and further collaborative work is crucial to address this question.

Keywords : next generation sequencing management genomic capture candidate genes breast and ovarian cancer susceptibility genes

Type de document :

Article dans une revue

Domaine :

Sciences du Vivant [q-bio] / Biologie cellulaire

Sciences du Vivant [q-bio] / Cancer

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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01527309
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 24 mai 2017 - 11:18:57
Dernière modification le : jeudi 11 juin 2020 - 04:30:53

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

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The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

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