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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-8-30
pubmed:abstractText
Disruption of the APC/beta-catenin/Tcf pathway has been proposed as an important step in the development of cancer. The Tcf-4 transcription factor gene was reported to be one of the targets of microsatellite instability (MSI) in colorectal cancers in with MSI. We carried out a sequencing analysis of the Tcf-4 gene in 41 Japanese patients with gastrointestinal tumors with MSI as well as in cancer cell lines. Three of 21 (14.3%) colorectal tumors with MSI contained a mutant Tcf-4 gene encoding 1-bp deletion in an (A)9 repeat, leading to carboxyl terminal truncation of Tcf-4 protein. No Tcf-4 mutations were detected in 20 gastric tumors with MSI, or in gastric cancer cell lines. Additionally, we found a novel transcript of the Tcf-4 gene which contained a segment of 73 bp in front of the (A)9 repeat of the Tcf-4 coding sequence. Sequencing analysis revealed that the inserted fragment was 60% homologous to that of exon IXA of the Tcf-1 gene. It is of interest that this insertion resulted in truncation of Tcf-4, similar to the 1-bp deletion in the (A)9 repeat. Therefore, in part of the Japanese colorectal tumors with MSI, frameshift mutations in Tcf-4 may be of functional significance. Functional alterations in the Tcf-4 signaling network in gastrointestinal tumorigenesis require further investigations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0030-2414
pubmed:author
pubmed:copyrightInfo
Copyright 2001 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
156-61
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11528255-Adenocarcinoma, pubmed-meshheading:11528255-Alternative Splicing, pubmed-meshheading:11528255-Amino Acid Sequence, pubmed-meshheading:11528255-Base Sequence, pubmed-meshheading:11528255-Colorectal Neoplasms, pubmed-meshheading:11528255-DNA, Neoplasm, pubmed-meshheading:11528255-DNA Mutational Analysis, pubmed-meshheading:11528255-Gastrointestinal Neoplasms, pubmed-meshheading:11528255-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11528255-Humans, pubmed-meshheading:11528255-Japan, pubmed-meshheading:11528255-Microsatellite Repeats, pubmed-meshheading:11528255-Molecular Sequence Data, pubmed-meshheading:11528255-Neoplasm Proteins, pubmed-meshheading:11528255-Protein Isoforms, pubmed-meshheading:11528255-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11528255-Sequence Alignment, pubmed-meshheading:11528255-Sequence Analysis, DNA, pubmed-meshheading:11528255-Sequence Deletion, pubmed-meshheading:11528255-Sequence Homology, Amino Acid, pubmed-meshheading:11528255-Stomach Neoplasms, pubmed-meshheading:11528255-TCF Transcription Factors, pubmed-meshheading:11528255-Transcription Factor 7-Like 2 Protein, pubmed-meshheading:11528255-Transcription Factors, pubmed-meshheading:11528255-Transcriptional Activation, pubmed-meshheading:11528255-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic gastrointestinal cancers with microsatellite instability.
pubmed:affiliation
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. hsaeki@med.kyushu-u.ac.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't