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 microarrays.


METHODS
Whole-genome analysis of mRNA levels in leiomyoma and normal myometrium tissue samples.


METHODS
University research laboratory.


METHODS
Eight patients of varying age and race undergoing surgery for symptomatic fibroids.


METHODS
After tissue collection of five tumors and five normals from human pathological specimens, labeled cRNA was generated and hybridized to the oligonucleotide-composed arrays.


METHODS
Quantification of transcript expression levels in uterine fibroids relative to normal myometrium.


RESULTS
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.


CONCLUSIONS
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.
Hoffman
Paul J
PJ
Department of Pathology, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
Milliken
Dawn B
DB
Gregg
Laurie C
LC
Davis
Ryan R
RR
Gregg
Jeffrey P
JP
D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D007889:Leiomyoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008597:Menstrual Cycle; D009215:Myometrium / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery