T-cell factor-4 frameshift mutations occur frequently in human microsatellite instability-high colorectal carcinomas but do not contribute to carcinogenesis.
Colorectal carcinomas with microsatellite instability accumulate errors in short repetitive DNA repeats, especially mono and dinucleotide repeats. One such error-prone A(9) monorepeat is found in exon 17 of the TCF-4 gene. TCF-4 and beta-catenin form a transcription complex, which is important for both maintenance of normal epithelium and development of colorectal tumors. To elucidate the relevance of frameshift mutations in the TCF-4 in colorectal carcinogenesis, a variety of investigations in human tumors and cell lines was performed. It was found that mutations in the TCF-4 A(9) repeat do not contribute to tumorigenesis and seem to be passenger mutations.
Ruckert
Stefan
S
Pathologisches Institut, der Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 8-10, D-91054 Erlangen, Germany.
Hiendlmeyer
Elke
E
Brueckl
Wolfgang M
WM
Oswald
Ursula
U
Beyser
Kurt
K
Dietmaier
Wolfgang
W
Haynl
Angela
A
Koch
Claudia
C
Rüschoff
Josef
J
Brabletz
Thomas
T
Kirchner
Thomas
T
Jung
Andreas
A
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D016296:Mutagenesis; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin