Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas. Gynecol Oncol 2010 May;117(2):239-47
Date
03/10/2010Pubmed ID
20211485Pubmed Central ID
PMC2849881DOI
10.1016/j.ygyno.2010.02.006Scopus ID
2-s2.0-77950188986 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
OBJECTIVE: DNA promoter methylation is an epigenetic phenomenon for long-term gene silencing during tumorigenesis. The purpose of this study is to identify novel hypermethylated loci associated with clinicopathologic variables in endometrioid endometrial carcinomas.
METHODS: To find hypermethylated promoter loci, we used differential methylation hybridization coupling with microarray and further validated by combined bisulfite restriction analysis and MassARRAY assay. Methylation levels of candidate loci were corrected with clinicopathologic factors of endometrial carcinomas.
RESULTS: Increased promoter methylation of CIDE, HAAO and RXFP3 was detected in endometrial carcinomas compared with adjacent normal tissues, and was associated with decreased gene expression of all three genes. In a clinical cohort, promoter hypermethylation on CIDEA, HAAO and RXFP3 was detected in 85, 63 and 71% of endometrial carcinomas, respectively (n=118, P<0.001) compared with uninvolved normal endometrium. Methylation status of CIDEA, HAAO and RXFP3 had significant association with microsatellite instability in tumors (P<0.001). Furthermore, methylation levels of HAAO were further found to relate to disease-free survivals (P=0.034).
CONCLUSIONS: Hypermethylation of CIDEA, HAAO and RXFP3 promoter regions appears to be a frequent event in endometrial carcinomas. Hypermethylation at these loci is strongly associated with microsatellite instability status. Moreover, HAAO methylation predicts disease-free survival in this cohort of patients with endometrioid endometrial cancer.
Author List
Huang YW, Luo J, Weng YI, Mutch DG, Goodfellow PJ, Miller DS, Huang THMESH terms used to index this publication - Major topics in bold
3-Hydroxyanthranilate 3,4-DioxygenaseApoptosis Regulatory Proteins
DNA Methylation
Endometrial Neoplasms
Female
Humans
Microsatellite Instability
Middle Aged
Promoter Regions, Genetic
RNA, Messenger
Receptors, G-Protein-Coupled
