The Intestinal Wnt/TCF Signature.
OBJECTIVE
In colorectal cancer, activating mutations in the Wnt pathway transform epithelial cells through the inappropriate expression of a TCF4 target gene program, which is physiologically expressed in intestinal crypts.


METHODS
We have now performed an exhaustive array-based analysis of this target gene program in colorectal cancer cell lines carrying an inducible block of the Wnt cascade. Independently, differential gene-expression profiles of human adenomas and adenocarcinomas vs normal colonic epithelium were obtained.


RESULTS
Expression analyses of approximately 80 genes common between these data sets were performed in a murine adenoma model. The combined data sets describe a core target gene program, the intestinal Wnt/TCF signature gene set, which is responsible for the transformation of human intestinal epithelial cells.


CONCLUSIONS
The genes were invariably expressed in adenomas, yet could be subdivided into 3 modules, based on expression in distinct crypt compartments. A module of 17 genes was specifically expressed at the position of the crypt stem cell.
Van der Flier
Laurens G
LG
Hubrecht Institute, Netherlands Institute for Developmental Biology and Centre for Biomedical Genetics, Utrecht, The Netherlands.
Sabates-Bellver
Jacob
J
Oving
Irma
I
Haegebarth
Andrea
A
De Palo
Mariagrazia
M
Anti
Marcello
M
Van Gijn
Marielle E
ME
Suijkerbuijk
Saskia
S
Van de Wetering
Marc
M
Marra
Giancarlo
G
Clevers
Hans
H
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D019879:Paneth Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051822:T Cell Transcription Factor 1 / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D058118:Transcription Factor 7-Like 2 Protein; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D012333:RNA, Messenger; D051822:T Cell Transcription Factor 1; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins; D051176:beta Catenin