National recommendations of the French Genetics Cancer Group – Unicancer on the modalities of multi-gene panel analyses in hereditary predispositions to tumours of the digestive tract

Chrystelle Colas1, Marion Dhooge2, Carole Corsini3, Nadine Andrieu4, Pascaline Berthet5, Valérie Bonadona6, Bruno Buecher1, Olivier Caron7, Odile Cohen-Haugenauer8, Antoine De Pauw1, Capucine Delnatte9, Sophie Dussart6, Christophe Jamain10, Dominique Leroux11, Christine Maugard12, Jessica Moretta Serra13, Cornel Popovici13, Christine Lasset6, Catherine Nogues13, Stéphanie Baert-Desurmont14

1Institut Curie, Paris, France. 2Cochin Hospital-APHP, Paris, France. 3Montpellier Hospital-Arnaud de Villeneuve hospital, Montpellier, France. 4Institut Curie- INSERM, Paris, France. 5Centre François Baclesse, Caen, France. 6Centre Léon Bérard, Lyon, France. 7Gustave Roussy Hospital, Villejuif, France. 8Saint Louis-Louis Hospital – APHP, Paris, France. 9ICO -Centre René Gauducheau, Nantes, France. 10Unicancer, Paris, France. 11Grenoble hospital, Grenoble, France. 12Strasbourg hospital, Strasbourg, France. 13Institut Paoli-Calmettes, Marseille, France. 14Charles Nicolle Hospital, Rouen, France


When inherited predisposition to digestive cancers is suspected, next-generation sequencing holds the potential to analyse at once a large number of genes. Thus, “digestive” gene panels are commonly used in French molecular genetic laboratories. Due to the lack of national recommendations, there are disparities in the composition of these panels and in the medical management of patients.

In order to harmonize practices, the Genetics Cancer Group (GGC)-Unicancer set up a working group of 19 experts who carried out an exhaustive review of the literature for 31 genes of interest addressing for familial digestive predispositions. The group identified publications with risk estimates and establish a list of genes with estimated levels of associated risk which seemed sufficiently reliable and high for clinical use.

We defined a panel of 14 genes of confirmed clinical interest in the context of inherited predisposition to cancers of the digestive tract (reliable estimates of tumour risks, associated monitoring recommendations and availability of pre-symptomatic genetic tests in relatives): APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, MUTYH (biallelic mutations), PMS2, POLD1, POLE, PTEN, SMAD4 and STK11. The lack of estimates of the associated tumour risks led to the exclusion of genes, in particular CTNNA1, MSH3 and NTHL1, despite their role in molecular pathways involved in digestive tract physiopathology.

An update of the literature will improve the selected panel of genes. Genetic and epidemiological studies are still needed to better estimate the risks associated with genes whether selected or not in the current panel.