Priority Research Papers:
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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Marie Eliade1,*, Jeremy Skrzypski2,*, Amandine Baurand1,2, Caroline Jacquot1,2, Geoffrey Bertolone1,2, Catherine Loustalot3, Charles Coutant3,18, France Guy4, Pierre Fumoleau5,18, Yannis Duffourd6, Laurent Arnould7, Alexandra Delignette8, Marie-Martine Padéano3, Côme Lepage9,17, Géraldine Raichon-Patru10, Axelle Boudrant11, Marie-Christine Bône-Lépinoy12, Anne-Laure Villing13, Aurélie Charpin1, Karine Peignaux14, Sandy Chevrier15, Frédérique Vegran15, François Ghiringhelli5,15, Romain Boidot15, Nicolas Sevenet16, Sarab Lizard7,*, Laurence Faivre1,2,*
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
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
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.
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