title: Aneuploidy-dependent massive deregulation of the cellular transcriptome and apparent divergence of the Wnt/beta-catenin signaling pathway in human rectal carcinomas.
abstract: To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P < 1.0e-7) between normal rectal mucosa and rectal carcinomas, 77 genes had a >5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, 18q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas.
authors.affiliation: Department of General Surgery, University Medical Center, Göttingen, Germany.
authors.forename: Marian
authors.initials: M
authors.lastname: Grade
authors.forename: B Michael
authors.initials: BM
authors.lastname: Ghadimi
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.forename: Danny
authors.initials: D
authors.lastname: Wangsa
authors.forename: Linda
authors.initials: L
authors.lastname: Barenboim-Stapleton
authors.forename: Torsten
authors.initials: T
authors.lastname: Liersch
authors.forename: Heinz
authors.initials: H
authors.lastname: Becker
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Difilippantonio
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000782:Aneuploidy; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D012004:Rectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051154:Wnt2 Protein / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D051154:Wnt2 Protein; D051176:beta Catenin