title: Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes.
abstract: BACKGROUND
  In addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups.
  
  
  METHODS
  DNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16) or aneuploid (n = 9), and all uterine papillary serous cancers (UPSC) to be aneuploid (n = 8). All samples were subjected to comparative genomic hybridization and gene expression profiling. Identified genes were subjected to Ingenuity pathway analysis (IPA) and were correlated to protein expression changes.
  
  
  RESULTS
  Comparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. Gene expression analysis identified 54 genes between diploid and aneuploid endometrioid carcinomas, 39 genes between aneuploid endometrioid cancer and UPSC, and 76 genes between diploid endometrioid and aneuploid UPSC to be differentially expressed. Protein profiling identified AKR7A2 and ANXA2 to show translational alterations consistent with the transcriptional changes. The majority of differentially expressed genes and proteins belonged to identical molecular functions, foremost Cancer, Cell Death, and Cellular Assembly and Organization.
  
  
  CONCLUSIONS
  We conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. The identified genes and proteins might be useful as molecular targets for improved diagnostic and therapeutic intervention and merit prospective validation.
authors: Laboratory for Surgical Research, Department of Surgery, University of Lübeck, Germany. Jens.Habermann@gmail.com
authors: Jens K
authors: JK
authors: Habermann
authors: Nana K
authors: NK
authors: Bündgen
authors: Timo
authors: T
authors: Gemoll
authors: Sampsa
authors: S
authors: Hautaniemi
authors: Caroline
authors: C
authors: Lundgren
authors: Danny
authors: D
authors: Wangsa
authors: Jana
authors: J
authors: Doering
authors: Hans-Peter
authors: HP
authors: Bruch
authors: Britta
authors: B
authors: Nordstroem
authors: Uwe J
authors: UJ
authors: Roblick
authors: Hans
authors: H
authors: Jörnvall
authors: Gert
authors: G
authors: Auer
authors: Thomas
authors: T
authors: Ried
mesh_terms: D000782:Aneuploidy; D016889:Endometrial Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D020543:Proteome / Q000235:genetics*; D059467:Transcriptome
chemical_list: D020543:Proteome