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)