MSI-H can occur in inherited syndromes like Lynch syndrome, caused by mutations in MMR genes (MLH1, MSH2, MSH6, PMS2) or EPCAM genes, or from sporadic somatic mutations, often due to epigenetic silencing of MLH1 through promoter hypermethylation, the leading mechanism of MMR loss in both sporadic and familial MSI-H GC cases [33]. This evidence concerns the gene MRC1 and Lynch syndrome.