The French Genetic and Cancer Consortium guidelines for multigene panel analysis in hereditary breast and ovarian cancer predisposition

Jessica Moretta , Pascaline Berthet , Valerie Bonadona , Olivier Caron , Odile Cohen-Haguenauer , Chrystelle Colas , Carole Corsini , Veronica Cusin , Antoine de Pauw , Capucine Delnatte , Sophie Dussart , Christophe Jamain , Michel Longy , Elisabeth Luporsi , Christine Maugard , Tan Dat Nguyen , Pascal Pujol , Dominique Vaur , Nadine Andrieu , Christine Lasset , Catherine Nogues (1) , Grp Genetique Canc Unicanc

1 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale

Introduction > Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed. Methods > The French Genetic and Cancer Group (GGC) - Uniconcer conducted an exhaustive bibliographic work on 18 genes of interest. Only publications with unbiased risk estimates were retained. Results > The expertise of each 18 genes was based on clinical utility criteria, i.e. a relative risk of cancer of 4 and more, available medical tools for screening and prevention of mutation carriers, and pre-symptomatic genetic tests for relatives. Finally, 13 genes were selected to be included in a HBOC diagnosis gene panel: BRCA1, BRCA2, PALB2, TP53, CDPH1, PTEN, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM. The reasons for excluding NBN, RAD51B, CHEK2, STK11, ATM, BARD1, BRIP1 from the HBOC diagnosis panel are presented. Screening, prevention and genetic counselling guidelines were detailed for each of the 18 genes. Discussion > Due to the rapid increase in knowledge, the GGC has planned a yearly update of the bibliography to take into account new findings. Furthermore, genetic-epidemiological studies are being initiated to better estimate the cancer risk associated with genes which are not yet included in the HBOC diagnosis panel.

Domaines: Sciences du Vivant [q-bio]

Jessica Moretta, Pascaline Berthet, Valerie Bonadona, Olivier Caron, Odile Cohen-Haguenauer, et al.. The French Genetic and Cancer Consortium guidelines for multigene panel analysis in hereditary breast and ovarian cancer predisposition. Bulletin du Cancer, 2018, 105 (10), pp.907-917. ⟨10.1016/j.bulcan.2018.08.003⟩. ⟨hal-02146849⟩