Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: new evidence and a systematic review.
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.
Arslan
Alan A
AA
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
Gold
Leslie I
LI
Mittal
Khushbakhat
K
Suen
Ting-Chung
TC
Belitskaya-Levy
Ilana
I
Tang
Moon-Shong
MS
Toniolo
Paolo
P
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*