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Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis
Paul J Hoffman1, Dawn B Milliken, Laurie C Gregg
1Department of Pathology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
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 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 > or =1.5-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.