Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis

Objective: To identify genes involved in fibroid development by performing global expression profiling on tissues of normal myometrium and uterine leiomyoma origin using Affymetrix HG-U133A GeneChip((R)) microarrays. Design: Whole-genome analysis of mRNA levels in leiomyoma and normal myometrium tissue samples. Setting: University research laboratory. Patient(s): Eight patients of varying age and race undergoing surgery for symptomatic fibroids. Intervention(s): After tissue collection of five tumors and five normals from human pathological specimens, labeled cRNA was generated and hybridized to the oligonucleotide-composed arrays. Main Outcome Measure(s): Quantification of transcript expression levels in uterine fibroids relative to normal myometrium. Result(s): Model-based expression analysis revealed that of the 22,500 transcripts represented on the arrays, 226 genes were found to be dysregulated by a greater than or equal to1.5-fold change between leiomyoma and normal myometrium. Moreover, our research identified many dysregulated apoptosis-related genes, of particular interest was TRAIL and Ask1, and also found numerous differentially expressed proliferation genes, including TGFB1, PDGFC, and two dual specificity phosphatases. Conclusion(s): These results indicate that these genes may play a significant role in the development of leiomyomas from normal uterine tissue. We hypothesize that the deregulation of apoptotic and proliferative processes is pivotal to fibroid development. (C) 2004 by American Society for Reproductive Medicine.