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Research Resource: Gene Expression Profile for Ectopic Versus Eutopic Endometrium Provides New Insights into Endometriosis Oncogenic Potential

Institut Cochin (B.B., F.M., T.-M.M., D.V., C.C.), Université Paris Descartes, Centre National de la Recherche Scientifique (Unité Mixte de Recherche 8104), and Institut National de la Santé et de la Recherche Médicale (B.B., F.M., T.-M.M., D.V., C.C.), Unité 567, 75014 Paris, France; Service de Gynécologie-Obstétrique 2 et Médecine de la Reproduction (B.B., C.C.), Centre Hospitalier Universitaire Cochin Saint-Vincent de Paul, Assistance Publique-Hôpitaux de Paris, 75674 Paris, France; and Department of Pathology (J.-C.N., I.F.), Erasme University Hospital, Free University of Brussels, B-1070 Brussels, Belgium

Address all correspondence and requests for reprints to: Dr. Bruno Borghese, Equipe 21, Département Génétique et Développement, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail: bruno.borghese{at}inserm.fr.

ABSTRACT

Endometriosis is a common gynecological disorder characterized by pain and infertility, where the lesions disseminate everywhere in the body with a preference for the pelvis. In that, it could be regarded as a benign metastatic disease, because its issue is not fatal. However, the molecular bases of this intriguing clinical condition are not well known. The objective of this study is to characterize the transcriptome differences between eutopic vs. ectopic endometrium with a special interest in pathways involved in cancerogenesis. We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGen), with cDNA prepared from six-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas). To confirm the expression microarrays data, quantitative RT-PCR validation was performed on 12 individuals for 20 genes. Over 8000 transcripts were significantly modified (more than twice) in the lesions corresponding to 5600 down- or up-regulated genes. These were clustered through DAVID Bioinformatics Resources into 55 functional groups. The data are presented in a detailed and visual way on 24 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways implemented with induction ratios for each differentially expressed gene. An outstanding control of the cell cycle and a very specific modulation of the HOX genes were observed and provide some new evidence on why endometriosis only very rarely degenerates into cancer. The study constitutes a noteworthy update of gene profiling in endometriosis, by delivering the most complete and reliable list of dysregulated genes to date.

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