Microsatellite instability(MSI) in non-small cell lung cancer(NSCLC) is highly associated with transforming growth factor-beta type II receptor(TGF-beta RII) frameshift mutation

Anticancer Res. 2000 May-Jun;20(3A):1499-502.

Abstract

Background: TGF-beta type II receptor (TGF-beta RII) mutations associated with microsatellite instability(MSI) are characteristically frameshift mutations within a 10 bp poly-A tract. These frameshift mutations have been reported to be common in colorectal and gastric cancers with MSI, though, rarely reported in non-small cell lung cancer (NSCLC).

Materials and method: In this study, we analysed MSI and TGF-beta RII frameshift mutations in 7 NSCLC cell lines and 21 surgically resected NSCLC tissues. Determination of MSI in NSCLC was performed using primer sets for BAT-25, BAT-26 and BAT-40. In order to examine the presence of the frameshift mutations of TGF-beta RII in samples with MSI, sequencing for TGF-beta RII poly-A tract was performed.

Results: MSI was observed in 5 out of 7 NSCLC cell lines and 3 out of 21 NSCLC tissues. Six out of 8 samples with MSI(75%) showed frameshift mutations in TGF-beta RII poly-A tract.

Conclusion: These results suggest that MSI is highly associated with TGF-beta RII frameshift mutations in NSCLC and further support the hypothesis that TGF-beta RII plays an important role in NSCLC carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA, Neoplasm / analysis
  • Frameshift Mutation
  • Humans
  • Lung Neoplasms / genetics*
  • Microsatellite Repeats / genetics*
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II