Mutations in MMR genes (MLH1)
MLH1 (mutL Homology 1) gene, located on 3p21.3, encodes a protein that plays an essential role in DNA repair. MLH1 protein forms a complex with the protein encoded by the PMS2 gene, and the active complex coordinates the activities of other proteins that repair errors made during DNA replication. More than 100 mutations had been found in this gene, and approximately 50% of all cases of Lynch syndrome are associated with mutations in MLH1. Patients carrying mutations in this gene are also more likely to develop other cancers, including endometrium, ovary, stomach, small intestine, liver, gallbladder, upper urinary tract and brain cancer. MLH1 gene mutations can cause Turcot syndrome, a variant of Lynch syndrome, where brain glioblastoma appears in addition to colorectal cancer. When homozygous mutations are present in both chromosomes, in addition to colorectal cancer the patient may develop leukemia or lymphoma, and other non-cancerous conditions such as neurofibromatosis. In this group of patients colorectal cancer appears early in childhood (CoLoN syndrome: Colon cancer, Leukemia or Lymphoma, and Neurofibromatosis).
