title: Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review.
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 Affymetrix 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 > or = 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.
authors.affiliation: Department of Obstetrics & Gynecology, Department of Environmental Medicine, Department of Pathology and Department of Medicine, New York University School of Medicine, New York, NY 10016, USA. akhmea01@med.nyu.edu
authors.forename: Alan A
authors.initials: AA
authors.lastname: Arslan
authors.forename: Leslie I
authors.initials: LI
authors.lastname: Gold
authors.forename: Khushbakhat
authors.initials: K
authors.lastname: Mittal
authors.forename: Ting-Chung
authors.initials: TC
authors.lastname: Suen
authors.forename: Ilana
authors.initials: I
authors.lastname: Belitskaya-Levy
authors.forename: Moon-Shong
authors.initials: MS
authors.lastname: Tang
authors.forename: Paolo
authors.initials: P
authors.lastname: Toniolo
mesh_terms: D000328:Adult; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000209:etiology / Q000235:genetics*