title: Aberrant DNA methylation status in human uterine leiomyoma.
abstract: Aberrant DNA methylation has been implicated in tumorigenesis. This study was undertaken to establish the genome-wide DNA methylation profile in uterine leiomyomas and to investigate whether DNA methylation status is altered in uterine leiomyomas. For this purpose, restriction landmark genomic scanning (RLGS) was performed on a paired sample of leiomyoma and adjacent normal myometrium. The RLGS profile revealed 29 aberrant methylation spots (10 methylated and 19 demethylated) in leiomyoma in comparison with myometrium. One of the differently methylated genomic loci was newly identified as GS20656 from the human genome sequence database. In 9 of the 10 paired samples, the DNA methylation levels of the first exon of GS20656 were significantly lower in leiomyoma than in myometrium, suggesting the existence of a genomic locus under epigenetic regulation in uterine leiomyomas. Unexpectedly, DNA methyltransferase 1 (DNMT1) and DNMT3a mRNA expression levels were higher in leiomyoma than in myometrium. These facts suggest that other epigenetic factors besides DNMT are involved in local changes of DNA methylation at genome loci. The present study indicates not only aberrant genome-wide DNA methylation status in uterine leiomyomas but also the existence of a genomic locus that is differently methylated between normal myometrium and uterine leiomyoma.
authors.affiliation: Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Ryo
authors.initials: R
authors.lastname: Maekawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Asada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Taketani
authors.forename: Isao
authors.initials: I
authors.lastname: Tamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.forename: Jun
authors.initials: J
authors.lastname: Ogane
authors.forename: Naka
authors.initials: N
authors.lastname: Hattori
authors.forename: Kunio
authors.initials: K
authors.lastname: Shiota
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sugino
mesh_terms: D000328:Adult; D044466:Asian People; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D015894:Genome, Human; D006801:Humans; D007889:Leiomyoma / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D009215:Myometrium / Q000201:enzymology / Q000502:physiology; D014594:Uterine Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: D015254:DNA Modification Methylases