Most of these patients do not have a germline mutation, but a loss of expression is due to somatic biallelic hypermethylation of the MLH1 promoter, as reported for CRC [44], to somatic biallelic MMR gene mutations, or to a somatic mutation associated with a loss of heterozygosity (LOH) of the other allele; alternatively, it is due to a secondary epigenetic silencing of MSH6 after neoadjuvant radio-chemotherapy treatments. The gene discussed is MSH6; the disease is colorectal carcinoma.