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, Tim H.M. Huang

Producción científica: Articlerevisión exhaustiva

40 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)239-247
Número de páginas9
PublicaciónGynecologic Oncology
Volumen117
N.º2
DOI
EstadoPublished - may 2010
Publicado de forma externa

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

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