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 2,* , Amandine Baurand 1,2 , Caroline Jacquot 1,2 , Geoffrey Bertolone 1,2 , Catherine Loustalot 3 , Charles Coutant 3,18 , France Guy 4 , Pierre Fumoleau 5,18 , Yannis Duffourd 6 , Laurent Arnould 7 , Alexandra Delignette 8 , Marie-Martine Padéano 3 , Côme Lepage 9,17 , Géraldine Raichon-Patru 10 , Axelle Boudrant 11 , Marie-Christine Bône-Lépinoy 12 , Anne-Laure Villing 13 , Aurélie Charpin 1 , Karine Peignaux 14 , Sandy Chevrier 15 , Frédérique Vegran 15 , François Ghiringhelli 5,15 , Romain Boidot 15 , Nicolas Sevenet 16 , Sarab Lizard 7,* , Laurence Faivre 1,2,* 1 Centre of Genetic, Children Hospital, CHU, Dijon, France 2 Oncogenetic Unit, Centre Georges-François Leclerc Centre, Dijon, France 3 Gynecological Surgery, Georges-François Leclerc Centre, Dijon, France 4 Radiology unit, Georges-François Leclerc Centre, Dijon, France 5 Medical Oncology, Georges-François Leclerc Centre, Dijon, France 6 Orphanomix, Dijon, France 7 Biology and Tumor Pathology Department, Georges-François Leclerc Centre, Dijon, France 8 Elithis Tower, Radiology, Dijon, France 9 Hepato-Gastroenterology and Digestive Oncology, François Mitterand Hospital, CHU, Dijon, France 10 Oncology, Les Chanaux Hospital, Macon, France 11 Oncology, William Morey Hospital, Chalon-sur-Saône, France 12 Oncology, Drevon Clinic, Dijon, France 13 Oncology, Hospital, Auxerre, France 14 Radiotherapy Unit, Georges-François Leclerc Centre, Dijon, France 15 Platform of Transfer in Cancer Biology, Georges-François Leclerc Centre, Dijon, France 16 Bergonié Institute, Bordeaux, France 17 Burgundy Franche-Comté University, INSERM LNC UMR866, Dijon, France 18 Burgundy Franche-Comté University, Dijon, France * These authors have contributed equally to this work Correspondence to: Laurence Faivre, email: // Keywords : next generation sequencing; breast and ovarian cancer susceptibility genes; genomic capture; candidate genes; management Received : March 08, 2016 Accepted : August 13, 2016 Published : October 15, 2016 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.