MLH1 and Leigh syndrome: Sporadic dMMR tumours arise due to epigenetic silencing of the MLH1 gene, representing approximately 12% of all CRCs; a hereditary subset termed Lynch Syndrome (LS)) arise from constitutional mutations in the MMR genes (MLH1, MSH2, MSH6, PMS2) or the EpCAM gene upstream of MSH2, conservatively representing 2–3% of CRC cases5,7.