title: Transcriptome profile of human colorectal adenomas.
abstract: Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the beta-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Jacob
authors.initials: J
authors.lastname: Sabates-Bellver
authors.forename: Laurens G
authors.initials: LG
authors.lastname: Van der Flier
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: de Palo
authors.forename: Elisa
authors.initials: E
authors.lastname: Cattaneo
authors.forename: Caroline
authors.initials: C
authors.lastname: Maake
authors.forename: Hubert
authors.initials: H
authors.lastname: Rehrauer
authors.forename: Endre
authors.initials: E
authors.lastname: Laczko
authors.forename: Michal A
authors.initials: MA
authors.lastname: Kurowski
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: Mirco
authors.initials: M
authors.lastname: Menigatti
authors.forename: Judith
authors.initials: J
authors.lastname: Luz
authors.forename: Teresa V
authors.initials: TV
authors.lastname: Ranalli
authors.forename: Vito
authors.initials: V
authors.lastname: Gomes
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pastorelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Faggiani
authors.forename: Marcello
authors.initials: M
authors.lastname: Anti
authors.forename: Josef
authors.initials: J
authors.lastname: Jiricny
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Marra
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; D012333:RNA, Messenger