Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas

Yi Wen Huang, Jingqin Luo, Yu I. Weng, David G. Mutch, Paul J. Goodfellow, David S. Miller, Hui-ming Huang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalGynecologic Oncology
Volume117
Issue number2
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Microsatellite Instability
Endometrial Neoplasms
Methylation
Disease-Free Survival
Endometrioid Carcinoma
Gene Silencing
DNA Methylation
Endometrium
Genetic Promoter Regions
Epigenomics
Carcinogenesis
Gene Expression
Genes
Neoplasms

Keywords

  • CIDEA
  • Endometrial carcinoma
  • HAAO
  • Hypermethylation
  • RXFP3

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas. / Huang, Yi Wen; Luo, Jingqin; Weng, Yu I.; Mutch, David G.; Goodfellow, Paul J.; Miller, David S.; Huang, Hui-ming.

In: Gynecologic Oncology, Vol. 117, No. 2, 05.2010, p. 239-247.

Research output: Contribution to journalArticle

Huang, Yi Wen ; Luo, Jingqin ; Weng, Yu I. ; Mutch, David G. ; Goodfellow, Paul J. ; Miller, David S. ; Huang, Hui-ming. / Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas. In: Gynecologic Oncology. 2010 ; Vol. 117, No. 2. pp. 239-247.
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abstract = "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.",
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AU - Luo, Jingqin

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AU - Goodfellow, Paul J.

AU - Miller, David S.

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N2 - 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.

AB - 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.

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