ECDB-Endometrial cancer gene database

REFERENCES

Gene Name	Gene ID	Pubmed ID	Classification	Mechanism	Marker	Type	Normal Cases	Disease Cases	Age	Mean Age	Place	FIGO	Grade	Remark	Title	Journal	Volume	Year
MLH1	4292	10072435	-	Hypermethylation	-	-	-	64	-	-	-	-	-	[1] MSH2 gene may contribute substantially to inherited forms of endometrial cancer. [2] The MLH1 promoter was methylated in 41 of 53 (77%) MSI-positive cancers investigated. In MSI-negative tumors on the other hand; there was evidence for limited methylation in only one of 11 tumors studied. Immunohistochemical investigation of a subset of the tumors revealed that methylation of the MLH1 promoter in MSI-positive tumors was associated with loss of MLH1 expression.	MLH1 promoter methylation and gene silencing is the primary cause of microsatellite instability in sporadic endometrial cancers	Human Molecular Genetics	8(4):661-6	1999
MLH1	4292	10550333	-	Hypermethylation	-	-	62 simple endometrial hyperplasia + 33 complex endometrial hyperplasia without atypia + 21 complex endometrial hyperplasia with atypia	27	-	-	-	-	-	[1] The hypermethylation of hMLH1 can be an early event in the pathogenesis of EC; preceding the development of an apparent MSI phenotype in a subset of cases. [2] 1 of 12 (91%) cases of endometrial carcinoma (EC) displaying MSI had hMLH1 promoter hypermethylation; whereas aberrant methylation of any of the other mismatch repair genes was not observed. All 15 cases of EC without MSI were unmethylated at hMLH1. Abnormal methylation of hMLH1 was also present in 8 of 116 (7%) cases of EH and was restricted primarily to the atypical endometrial hyperplasia (AEH) type with coexisting endometrial carcinoma. [3] 11 of 27 (40%) UECs had promoter hypermethylation of the hMLH1 gene. Moreover; when the EC samples were decoded for their MSI phenotype; hMLH1 was hypermethylated in 11 of 12 (91%) MSI+ tumors; whereas none of 15 MSI? tumors demonstrated hMLH1 promoter hypermethylation.	hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis.	The Americal Journal of Pathology	155(5):1767-72	1999
MLH1	4292	12700670	-	Hypermethylation	-	-	-	-	-	-	-	-	-	[1] hypermethylation of the MLH1 promoter is frequent in the histologically normal endometrium adjacent to cancers; supporting the notion that hypermethylation of mismatch repair genes is the initial step that triggers various genetic events in endometrial carcinogenesis. [2] The profile of CpG methylation in a wide range of MLH1 promoters in endometrial cancers and in the normal endometrium is largely unknown. The study investigates the region 700 bp upstream of MLH1 covering 48 CpG sites using bisulfite sequencing. Methylation status was classified as full (over 80% of CpGs are methylated); partial (10-80%) or nonmethylation (less than 10%). Of 56 endometrioid endometrial cancers; 16 (29%) were fully methylated; 14 (25%) were partially methylated and 26 (46%) were not methylated. Analyses of MLH1 by immunohistochemical means and of MSI revealed that the degree; rather than region-specific methylation of CpG islands is critical for decreased MLH1 expression and the MSI phenotype.	Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers	Oncogene	22(15):2352-60	2003