French recommendations on multi-gene panel testing in renal cell carcinoma

Renal cancers are inherited in about 5 % of cases and are associated with several genetic syndromes. Genetic testing is recommended for selected patients suspected of having hereditary syndromes. In the absence of guidelines regarding which genes should be included for carrying out genetic screening of these individuals, discrepancies existed among the next generation sequencing (NGS) multi-gene panels (MGP) used in French laboratories. There was therefore a clear need to standardise practices and offer patients with renal cancer a consensus-based genetic testing in France.

A working group comprising national experts from the French Genetic and Cancer Group Unicancer (GGC) and from the French network on Hereditary PREDIspositions to Renal Cancer (PREDIR) and encompassing medical geneticists, genetic counsellor, molecular biologists and epidemiologists was established. The objective was to define a list of clinically relevant genes that should be included in a "GGC-PREDIR" approved NGS MGP for patients with renal cancer. A list of 32 genes of interest was compiled following an exhaustive and critical review of the literature. The inclusion or exclusion of each gene was determined based on available data regarding risk, prevalence and analyses published from large studies of patients.

The French group of experts defined a list of 12 genes of clinical and genetic counselling relevance comprising BAP1, FH, FLCN, MET, PTEN, SDHA, SDHB, SDHC, SDHD, TSC1, TSC2 and VHL to be included in the national recommended "renal cancer" NGS MGP. For each of these genes, recommendations for renal surveillance are proposed.

Unlike hereditary predisposition to breast or colon cancer, hereditary renal cancer predispositions are rare syndromes and risk estimates are lacking for most of them. Prospective studies are needed to improve our knowledge. The GGC-PREDIR experts retained 12 genes for inclusion in the NGS MGP for renal cancer patients. However, the panel will be expanded on the basis of regularly updated data from the medical literature.