title: 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?
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.
authors: Centre of Genetic, Children Hospital, CHU, Dijon, France.
authors: Marie
authors: M
authors: Eliade
authors: Oncogenetic Unit, Centre Georges-François Leclerc Centre, Dijon, France.
authors: Jeremy
authors: J
authors: Skrzypski
authors: Centre of Genetic, Children Hospital, CHU, Dijon, France.|Oncogenetic Unit, Centre Georges-François Leclerc Centre, Dijon, France.
authors: Amandine
authors: A
authors: Baurand
authors: Centre of Genetic, Children Hospital, CHU, Dijon, France.|Oncogenetic Unit, Centre Georges-François Leclerc Centre, Dijon, France.
authors: Caroline
authors: C
authors: Jacquot
authors: Centre of Genetic, Children Hospital, CHU, Dijon, France.|Oncogenetic Unit, Centre Georges-François Leclerc Centre, Dijon, France.
authors: Geoffrey
authors: G
authors: Bertolone
authors: Gynecological Surgery, Georges-François Leclerc Centre, Dijon, France.
authors: Catherine
authors: C
authors: Loustalot
authors: Gynecological Surgery, Georges-François Leclerc Centre, Dijon, France.|Burgundy Franche-Comté University, Dijon, France.
authors: Charles
authors: C
authors: Coutant
authors: Radiology Unit, Georges-François Leclerc Centre, Dijon, France.
authors: France
authors: F
authors: Guy
authors: Medical Oncology, Georges-François Leclerc Centre, Dijon, France.|Burgundy Franche-Comté University, Dijon, France.
authors: Pierre
authors: P
authors: Fumoleau
authors: Orphanomix, Dijon, France.
authors: Yannis
authors: Y
authors: Duffourd
authors: Biology and Tumor Pathology Department, Georges-François Leclerc Centre, Dijon, France.
authors: Laurent
authors: L
authors: Arnould
authors: Elithis Tower, Radiology, Dijon, France.
authors: Alexandra
authors: A
authors: Delignette
authors: Gynecological Surgery, Georges-François Leclerc Centre, Dijon, France.
authors: Marie-Martine
authors: MM
authors: Padéano
authors: Hepato-Gastroenterology and Digestive Oncology, François Mitterand Hospital, CHU, Dijon, France.|Burgundy Franche-Comté University, INSERM LNC UMR866, Dijon, France.
authors: Côme
authors: C
authors: Lepage
authors: Oncology, Les Chanaux Hospital, Macon, France.
authors: Géraldine
authors: G
authors: Raichon-Patru
authors: Oncology, William Morey Hospital, Chalon-sur-Saône, France.
authors: Axelle
authors: A
authors: Boudrant
authors: Oncology, Drevon Clinic, Dijon, France.
authors: Marie-Christine
authors: MC
authors: Bône-Lépinoy
authors: Oncology, Hospital, Auxerre, France.
authors: Anne-Laure
authors: AL
authors: Villing
authors: Centre of Genetic, Children Hospital, CHU, Dijon, France.
authors: Aurélie
authors: A
authors: Charpin
authors: Radiotherapy Unit, Georges-François Leclerc Centre, Dijon, France.
authors: Karine
authors: K
authors: Peignaux
authors: Platform of Transfer in Cancer Biology, Georges-François Leclerc Centre, Dijon, France.
authors: Sandy
authors: S
authors: Chevrier
authors: Platform of Transfer in Cancer Biology, Georges-François Leclerc Centre, Dijon, France.
authors: Frédérique
authors: F
authors: Vegran
authors: Medical Oncology, Georges-François Leclerc Centre, Dijon, France.|Platform of Transfer in Cancer Biology, Georges-François Leclerc Centre, Dijon, France.
authors: François
authors: F
authors: Ghiringhelli
authors: Platform of Transfer in Cancer Biology, Georges-François Leclerc Centre, Dijon, France.
authors: Romain
authors: R
authors: Boidot
authors: Bergonié Institute, Bordeaux, France.
authors: Nicolas
authors: N
authors: Sevenet
authors: Biology and Tumor Pathology Department, Georges-François Leclerc Centre, Dijon, France.
authors: Sarab
authors: S
authors: Lizard
authors: Centre of Genetic, Children Hospital, CHU, Dijon, France.|Oncogenetic Unit, Centre Georges-François Leclerc Centre, Dijon, France.
authors: Laurence
authors: L
authors: Faivre
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015331:Cohort Studies; D055317:Evidence-Based Practice; D005260:Female; D005602:France / Q000453:epidemiology; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000175:diagnosis* / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010817:Physician-Patient Relations; D017410:Practice Guidelines as Topic / Q000592:standards; D010818:Practice Patterns, Physicians' / Q000592:standards / Q000706:statistics & numerical data; D011368:Professional-Family Relations; D059467:Transcriptome; D057170:Translational Research, Biomedical / Q000592:standards / Q000706:statistics & numerical data
chemical_list: D014408:Biomarkers, Tumor
keywords: breast and ovarian cancer susceptibility genes; candidate genes; genomic capture; management; next generation sequencing