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Epigenome analysis of normal and cancer tissue from the uterine cervix

ABSTRACT: The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in normal and cancer tissue from the uterine cervix. There are a total of 63 samples, 15 samples of normal histology and 48 cervical cancers. The normal cervical samples were from women who underwent a hysterectomy for uterine fibroids. The 48 cervical cancers were from women who were treated at the Innsbruck Medical University between 1990 and 2006.

ORGANISM(S): Homo sapiens

PROVIDER: GSE30759 | GEO | 2012/02/23

SECONDARY ACCESSION(S): PRJNA154717

REPOSITORIES: GEO

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Project description:Uterine leiomyomata, or fibroids, are benign tumors of the uterine myometrium that significantly affect up to 30% of reproductive-age women. Despite being the primary cause of hysterectomy in the United States, accounting for up to 200,000 procedures annually, the etiology of leiomyoma remains largely unknown. Due to the lack of an effective medicinal therapy for these tumors, this disease continues to have a tremendous negative impact on women’s health. As a basis for understanding leiomyoma pathogenesis and identifying targets for pharmacotherapy, we conducted transcriptional profiling of leiomyoma and unaffected myometrium from humans and Eker rats, the best characterized preclinical model of leiomyoma. A global comparison of mRNA from leiomyoma versus myometrium in human and rat identified a highly significant overlap of dysregulated gene expression in leiomyoma. An unbiased pathway analysis using a method of gene set enrichment based on the Sigpathway algorithm detected the mammalian target of rapamycin (mTOR) pathway as one of the most highly upregulated pathways in both human and rat tumors. Activation of this pathway was confirmed in both human and rat leiomyomata at the protein level via Western. Inhibition of mTOR in female Eker rats with the rapamycin analog WAY-129327 for 2 weeks decreased mTOR signaling and cell proliferation in tumors, and treatment for 4 months significantly decreased tumor incidence, multiplicity and size. These results identify dysregulated mTOR signaling as a component of leiomyoma etiology across species and directly demonstrate the dependence of these tumors on mTOR signaling for growth in the Eker rat. Modulation of this pathway warrants additional investigation as a potential therapy for uterine leiomyoma. Experiment Overall Design: We analyzed 1-3 leiomyoma or normal myometrium biopsies from each 23 woman undergoing hysterectomy for the treatment of uterine fibroids. tment and compared it leiomyoma and normal myometrium from the Eker rat model of uterine fibroids (N=14-15)

Dataset Information

Epigenome analysis of normal and cancer tissue from the uterine cervix

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