Disease-dependent differently methylated regions (D-DMRs) of DNA are enriched on the X Chromosome in uterine leiomyoma

Ryo Maekawa, Shintaro Yagi, Jun Ohgane, Yoshiaki Yamagata, Hiromi Asada, Isao Tamura, Norihiro Sugino, Kunio Shiota

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16 Citations (Scopus)

Abstract

Uterine leiomyoma is the most common benign tumor in women. Although responsible gene mutations have not been found in leiomyomas, they represent a progressive disease with irreversible symptoms. To characterize epigenetic features of uterine leiomyomas, the DNA methylation status of a paired sample of leiomyoma and normal myometrium was subjected to a microarray-based DNA methylation analysis with restriction tag-mediated amplification (D-REAM). In the leiomyoma, we identified an aberrant DNA methylation status for 463 hypomethylated and 318 hypermethylated genes. Although these changes occurred on all chromosomes, aberrantly hypomethylated genes were preferentially located on the X chromosome. Using paired samples of normal myometrium and leiomyoma from 6 hysterectomy patients, methylation-sensitive quantitative real-time PCR revealed 14 shared X chromosome genes with an abnormal DNA hypomethylation status (FAM9A, CPXCR1, CXORF45, TAF1, NXF5, VBP1, GABRE, DDX53, FHL1, BRCC3, DMD, GJB1, AP1S2 and PCDH11X) and one hypermethylated locus (HDAC8). Expression of XIST, which is involved in X chromosome inactivation, was equivalent in the normal myometrium and leiomyoma, indicating that the epigenetic abnormality on the X chromosome did not result from aberration of XIST gene expression. Based on these data, a unique epigenetic signature for uterine leiomyomas has emerged. The 14 hypomethylated and one hypermethylated loci provide valuable biomarkers for understanding the molecular pathogenesis of leiomyoma.

Original languageEnglish
Pages (from-to)604-612
Number of pages9
JournalJournal of Reproduction and Development
Volume57
Issue number5
DOIs
Publication statusPublished - 2011 Jun 17
Externally publishedYes

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Keywords

  • Disease-dependent differently methylated regions (D-DMRs)
  • DNA methylation
  • Epigenetics
  • Leiomyoma
  • X chromosome

ASJC Scopus subject areas

  • Animal Science and Zoology

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