DNA hypomethylation and imbalanced expression of DNA methyltransferases (DNMT1, 3A, and 3B) in human uterine leiomyoma

Objective. Despite the high prevalence of uterine leiomyoma in women, little is known about the pathophysiology of this tumor. This study intends to define the epigenetic modulation of this tumor. Methods. Twenty-three pairs of leiomyomas and their adjacent myometria were collected. Status of DNA global methylation was determined by using DNA methyl acceptance assay and immunohistochemistry staining with 5-methylcytidine antibody. MRNA level of DNA methyltransferases (DNMT1, 3A, and 313) was assessed by quantitative real time PCR. Results. DNA global hypomethylation was detected in the leiomyoma tissues as compared with the adjacent myometria. DNMT1 expression was increased in 47.5% and was equal in 47.5% in leiomyomas compared to the adjacent myometria. On the other hand, over 74% of cases showed decreased expression of DNMT3A and 313 in leiomyomas compared to the adjacent myometria. Conclusion. Global hypomethylation and imbalanced expression of DNMTs in uterine leiomyoma suggested a potential mechanism of epigenetic modulation in the development of this tumor. (C) 2003 Elsevier Science (USA). All rights reserved.