Abstract
BackgroundThe pathogenesis of uterine leiomyomas, the most common benign tumor in women, remains unclear. Since acquired factors such as obesity, hypertension and early menarche place women at greater risk for uterine leiomyomas, uterine leiomyomas may be associated with epigenetic abnormalities that are caused by unfavorable environmental exposures.Principal FindingsProfiles of genome-wide DNA methylation and mRNA expression were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation and mRNA expression in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. We identified 120 genes whose DNA methylation and mRNA expression patterns differed between leiomyomas and the adjacent myometrium. The biological relevance of the aberrantly methylated and expressed genes was cancer process, including IRS1 that is related to transformation, and collagen-related genes such as COL4A1, COL4A2 and COL6A3. We also detected 22 target genes of estrogen receptor (ER) alpha, including apoptosis-related genes, that have aberrant DNA methylation in the promoter, suggesting that the aberrant epigenetic regulation of ER alpha-target genes contributes to the aberrant response to estrogen.ConclusionsAberrant DNA methylation and its related transcriptional aberration were associated with cancer processes, which may represent a critical initial mechanism that triggers transformation of a single tumor stem cell that will eventually develop into a monoclonal leiomyoma tumor. The aberrant epigenetic regulation of ER alpha-target genes also may contribute to the aberrant response to estrogen, which is involved in the development of uterine leiomyomas after menarche.
Highlights
Uterine leiomyomas are the most common uterine tumors in reproductive-age women with a prevalence of about 25% [1]
Aberrant DNA methylation and its related transcriptional aberration were associated with cancer processes, which may represent a critical initial mechanism that triggers transformation of a single tumor stem cell that will eventually develop into a monoclonal leiomyoma tumor
The aberrant epigenetic regulation of estrogen receptor (ER) alpha-target genes may contribute to the aberrant response to estrogen, which is involved in the development of uterine leiomyomas after menarche
Summary
Uterine leiomyomas are the most common uterine tumors in reproductive-age women with a prevalence of about 25% [1]. Factors that lower the risk include use of hormonal contraception, smoking, giving birth and consumption of green vegetables [3,4,5]. These findings suggest that both genetic and environmental factors are involved in the development of uterine leiomyomas. The pathogenesis of uterine leiomyomas, the most common benign tumor in women, remains unclear Since acquired factors such as obesity, hypertension and early menarche place women at greater risk for uterine leiomyomas, uterine leiomyomas may be associated with epigenetic abnormalities that are caused by unfavorable environmental exposures
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
