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Hum. Reprod. Advance Access published online on February 10, 2005
Human Reproduction, doi:10.1093/humrep/deh698
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Human Reproduction © European Society of Human Reproduction and Embryology 2005; all rights reserved
Received August 6, 2004
Revised October 11, 2004
Accepted November 30, 2004

Article

Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review

Alan A. Arslan 1*, Leslie I. Gold 2, Khushbakhat Mittal 3, Ting-Chung Suen 4, Ilana Belitskaya-Levy 4, Moon-Shong Tang 4, and Paolo Toniolo 5

1 Department of Obstetrics & Gynecology,, New York University School of Medicine, New York, NY, USA Department of Environmental Medicine,, New York University School of Medicine, New York, NY, USA
2 Department of Pathology and, New York University School of Medicine, New York, NY, USA Department of Medicine, New York University School of Medicine, New York, NY, USA
3 Department of Pathology and, New York University School of Medicine, New York, NY, USA
4 Department of Environmental Medicine,, New York University School of Medicine, New York, NY, USA
5 Department of Obstetrics & Gynecology,, New York University School of Medicine, New York, NY, USA Department of Environmental Medicine,, New York University School of Medicine, New York, NY, USA

* To whom correspondence should be addressed.
Alan A. Arslan, E-mail: akhmea01{at}med.nyu.edu


  Abstract

BACKGROUND: Uterine leiomyomas are extremely common and a major cause of pelvic pain, bleeding, infertility, and the leading indication for hysterectomy. Familial and epidemiological studies provide compelling evidence that genetic alterations play an important role in leiomyoma development. METHODS: Using AffymetrixTM U133A GeneChip we analysed expression profiles of 22 283 genes in paired samples of leiomyoma and adjacent normal myometrium. We compared our results with previously published data on gene expression in uterine leiomyoma and identified the overlapping gene alterations. RESULTS: We detected 80 genes with average differences of ≥2-fold and false discovery rates of <5% (14 overexpressed and 66 underexpressed). A comparative analysis including eight previous gene expression studies revealed eight prominent genes (ADH1, ATF3, CRABP2, CYR61, DPT, GRIA2, IGF2, MEST) identified by at least five different studies, eleven genes (ALDH1, CD24, CTGF, DCX, DUSP1, FOS, GAGEC1, IGFBP6, PTGDS, PTGER3, TYMS) reported by four studies, twelve genes (ABCA, ANXA1, APM2, CCL21, CDKN1A, CRMP1, EMP1, ESR1, FY, MAP3K5, TGFBR2, TIMP3) identified by three studies, and 40 genes reported by two different studies. CONCLUSIONS: Review of gene expression data revealed concordant changes in genes regulating retinoid synthesis, IGF metabolism, TGF-{beta} signaling and extracellular matrix formation. Gene expression studies provide clues to the relevant pathways of leiomyoma development.

Keywords: gene expression; leiomyoma; microarrays; myometrium; uterus.
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