MLH1 and Lynch syndrome: In hereditary nonpolyposis CCRs (e.g., Lynch syndrome), 90% of the MMR alterations are mainly due to constitutional mutations of the MLH1 and MSH2 gene (more rarely MSH6 or PMS2 gene) or alteration in EPCAM (TACSTD1) gene that causes epigenetic silencing of MSH2 [5, 6], while 10 to 15% of all sporadic CCRs are due to hypermethylation of CpG islands in the MLH1 promoter [6].