Novel genetic mutations detected by multigene panel are associated with hereditary colorectal cancer predisposition

Half of the high-risk colorectal cancer families (Amsterdam I-II and Bethesda criteria) tested for Lynch syndrome lack germline mutations in the mismatch repair (MMR) genes and remain unexplained. Genetic testing for hereditary cancers is rapidly evolving due to the introduction of multigene panels, which may identify more mutations than the old screening methods. This study use a NGS panel (targeting 94 genes involved in cancer predisposition) in order to find the genes involved in the cancer predisposition of these unexplained families. The detection of new pathogenic mutations in high and moderate penetrance genes could contribute to the explanation of the heritability of colorectal cancer, changing the individual clinical management. Multigene panel testing is a more effective method to identify germline variants in cancer patients compared to single-gene approaches.