RRC ID |
41420
|
著者 |
Saeki H, Tanaka S, Tokunaga E, Kawaguchi H, Ikeda Y, Maehara Y, Sugimachi K.
|
タイトル |
Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic gastrointestinal cancers with microsatellite instability.
|
ジャーナル |
Oncology
|
Abstract |
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.
|
巻・号 |
61(2)
|
ページ |
156-61
|
公開日 |
2001-1-1
|
DOI |
10.1159/000055367
|
PII |
55367
|
PMID |
11528255
|
MeSH |
Adenocarcinoma / ethnology
Adenocarcinoma / genetics*
Adenocarcinoma / pathology
Alternative Splicing
Amino Acid Sequence
Base Sequence
Colorectal Neoplasms / ethnology
Colorectal Neoplasms / genetics
Colorectal Neoplasms / pathology
DNA Mutational Analysis
DNA, Neoplasm / genetics
Gastrointestinal Neoplasms / ethnology
Gastrointestinal Neoplasms / genetics*
Gene Expression Regulation, Neoplastic
Humans
Japan / epidemiology
Microsatellite Repeats*
Molecular Sequence Data
Neoplasm Proteins / genetics*
Protein Isoforms / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Sequence Alignment
Sequence Analysis, DNA
Sequence Deletion
Sequence Homology, Amino Acid
Stomach Neoplasms / ethnology
Stomach Neoplasms / genetics
Stomach Neoplasms / pathology
TCF Transcription Factors
Transcription Factor 7-Like 2 Protein
Transcription Factors / genetics*
Transcriptional Activation
Tumor Cells, Cultured
|
IF |
2.642
|
引用数 |
8
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
MKN45(RCB1001)
MKN74(RCB1002)
NUGC-4(RCB1939) |