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Mol. Hum. Reprod. Advance Access originally published online on February 14, 2009
Molecular Human Reproduction 2009 15(4):259-267; doi:10.1093/molehr/gap010
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Aberrant DNA methylation status in human uterine leiomyoma

Yoshiaki Yamagata1, Ryo Maekawa1, Hiromi Asada1, Toshiaki Taketani1, Isao Tamura1, Hiroshi Tamura1, Jun Ogane2, Naka Hattori3, Kunio Shiota2 and Norihiro Sugino1,4

1Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan 2Laboratory of Cellular Biochemistry, Animal Resources/Veterinary Medical Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan 3Institute of Life Science, Ajinomoto Co., INC, 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8680, Japan

4 Correspondence address. Tel: +81-836-22-2286; Fax: +81-836-22-2287; E-mail: sugino{at}yamaguchi-u.ac.jp

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.

Key words: RLGS/DNA methylation/leiomyoma

Submitted on November 2, 2008; resubmitted on December 19, 2008; accepted on January 29, 2009.


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