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MIM.120436 3p21.3

Monday 29 September 2003

mismatch repair gene

MLH is homologous to the E. coli MutL gene and is involved in DNA mismatch repair. Mutations in the MLH1 gene result in hereditary nonpolyposis colorectal cancer-2 (HNPCC2) (MIM.609310).


Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by inherited germ line mutations in DNA mismatch repair genes, predominantly MSH2 and MLH1.

- MLH1 loss of expression

- MLH1 germline mutations

- MLH1 D132H variant is associated with susceptibility to sporadic colorectal cancer (15184898)

- germline epimutation of MLH1 in


- c.666dupA (16955466)

Somatic MLH1 hypermethylation

Somatic or germline GADD45A mutations did not explain sporadic MSI-H colon cancer.

Although germline MLH1 methylation was found in some individuals, locus-specific somatic MLH1 hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases.

Data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through somatic mutation of BRAF.

- Early onset MSI-H colon cancer with MLH1 promoter methylation (20444249).

See also

- MLHs


- Simpson AJ, Caballero OL, Pena SD. Microsatellite instability as a tool for the classification of gastric cancer. Trends Mol Med. 2001 Feb;7(2):76-80. PMID: 11286759

Open References

- Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition? van Roon EH, van Puijenbroek M, Middeldorp A, van Eijk R, de Meijer EJ, Erasmus D, Wouters KA, van Engeland M, Oosting J, Hes FJ, Tops CM, van Wezel T, Boer JM, Morreau H. BMC Cancer. 2010 May 5;10:180. PMID: 20444249 [Free]


- Plasilova M, Zhang J, Okhowat R, Marra G, Mettler M, Mueller H, Heinimann K. A de novo MLH1 germ line mutation in a 31-year-old colorectal cancer patient. Genes Chromosomes Cancer. 2006 Dec;45(12):1106-10. PMID: 16955466