Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic gastrointestinal cancers with microsatellite instability

Hiroshi Saeki, Shinji Tanaka, Eriko Tokunaga, Hidetoshi Kawaguchi, Yoichi Ikeda, Yoshihiko Maehara, Keizo Sugimachi

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10 Citations (Scopus)

Abstract

Disruption of the APC/β-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.

Original languageEnglish
Pages (from-to)156-161
Number of pages6
JournalOncology
Volume61
Issue number2
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Saeki, H., Tanaka, S., Tokunaga, E., Kawaguchi, H., Ikeda, Y., Maehara, Y., & Sugimachi, K. (2001). Genetic alterations in the human Tcf-4 gene in Japanese patients with sporadic gastrointestinal cancers with microsatellite instability. Oncology, 61(2), 156-161. https://doi.org/10.1159/000055367