BRAF and Lynch syndrome: Most MSI-high (MSI-H) tumors arise sporadically (4), often associated with hypermethylation of the MLH1 promoter or a mutation in BRAF V600E (specifically in colorectal cancer, CRC) (5), while others result from hereditary cancer predisposition syndromes such as Lynch syndrome [originated from a monoallelic germline mutation in one of the four major mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2, or the EPCAM gene] (6, 7).