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?

Content Provider	Europe PMC
Author	Eliade, Marie Skrzypski, Jeremy Baurand, Amandine Jacquot, Caroline Bertolone, Geoffrey Loustalot, Catherine Coutant, Charles Guy, France Fumoleau, Pierre Duffourd, Yannis Arnould, Laurent Delignette, Alexandra Padéano, Marie-Martine Lepage, Côme Raichon-Patru, Géraldine Boudrant, Axelle Bône-Lépinoy, Marie-Christine Villing, Anne-Laure Charpin, Aurélie Peignaux, Karine Chevrier, Sandy Vegran, Frédérique Ghiringhelli, François Boidot, Romain Sevenet, Nicolas Lizard, Sarab Faivre, Laurence
Copyright Year	2017
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.
Journal	Oncotarget
Volume Number	8
PubMed Central reference number	PMC5356770
Issue Number	2
PubMed reference number	27779110
e-ISSN	19492553
DOI	10.18632/oncotarget.12699
Language	English
Publisher	Impact Journals LLC
Publisher Date	2017-01-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2017 Eliade et al.
Subject Keyword	next generation sequencing breast and ovarian cancer susceptibility genes genomic capture candidate genes management
Content Type	Text
Resource Type	Article
Subject	Oncology