Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines

Tetsuya Mitsudomi, Eitan Friedman, Pablo V. Gejman, Frank McCormick, Adi F. Gazdar

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cell lines of non-small cell lung cancer (nonSCLC) have been shown to contain activating mutation of the K-ras oncogene in about 30% of cases, whereas no small cell lung cancer (SCLC) cell lines displayed these mutations. Biochemically, these mutations result in the ras gene product (p21) being constitutively activated in its GTP-bound form and insensitive to the hydrolytic action of the ras-specific GTPase-activating protein (ras GAP). We hypothesized that, if tumor development is related to the p21 ras being in the active GTP-bound state, then a similar malignant phenotype may result from an inactivating mutation in the ras GAP gene in the region that interacts with ras p21 (so-called catalytic domain). To test this hypothesis, we screened a panel of SCLC and non-SCLC cell lines for major genetic alterations in the catalytic domain of the GAP gene with the Sothern blot technique, and for minor genetic abnormalities (e.g., point mutations) with denaturing gradient gel electrophoresis and single-strand conformation polymorphism. Mutations in the catalytic domain of the GAP gene could not be demonstrated by any technique in any cell line examined. We conclude that mutational inactivation of the catalytic domain of the GAP gene probably does not contribute to the development of lung cancer.

Original languageEnglish (US)
Pages (from-to)27-31
Number of pages5
JournalHuman Genetics
Volume93
Issue number1
DOIs
StatePublished - Jan 1994

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Lung Neoplasms
Catalytic Domain
Cell Line
Mutation
ras GTPase-Activating Proteins
Proto-Oncogene Proteins p21(ras)
Genes
Small Cell Lung Carcinoma
Guanosine Triphosphate
Non-Small Cell Lung Carcinoma
Genetic Techniques
ras Proteins
Denaturing Gradient Gel Electrophoresis
ras Genes
Point Mutation
Phenotype
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Mitsudomi, T., Friedman, E., Gejman, P. V., McCormick, F., & Gazdar, A. F. (1994). Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines. Human Genetics, 93(1), 27-31. https://doi.org/10.1007/BF00218908

Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines. / Mitsudomi, Tetsuya; Friedman, Eitan; Gejman, Pablo V.; McCormick, Frank; Gazdar, Adi F.

In: Human Genetics, Vol. 93, No. 1, 01.1994, p. 27-31.

Research output: Contribution to journalArticle

Mitsudomi, T, Friedman, E, Gejman, PV, McCormick, F & Gazdar, AF 1994, 'Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines', Human Genetics, vol. 93, no. 1, pp. 27-31. https://doi.org/10.1007/BF00218908
Mitsudomi, Tetsuya ; Friedman, Eitan ; Gejman, Pablo V. ; McCormick, Frank ; Gazdar, Adi F. / Genetic analysis of the catalytic domain of the GAP gene in human lung cancer cell lines. In: Human Genetics. 1994 ; Vol. 93, No. 1. pp. 27-31.
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