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Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples

  1. Author:
    Angeloni, D.
    Danilkovitch-Miagkova, A.
    Ivanov, S. V.
    Breathnach, R.
    Johnson, B. E.
    Leonard, E. J.
    Lerman, M. I.

  2. Author Address

    Angeloni D NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab Frederick, MD 21702 USA Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Intramural Res Support Program Frederick, MD 21702 USA Inst Biol Nantes France NCI, USN, Med Branch, NIH Bethesda, MD 20892 USA
    1. Year: 2000
  2. Journal: Genes Chromosomes & Cancer
    1. 29
    2. 2
    3. Pages: 147-156
  4. Type of Article: Article
  1. Abstract:

    The human RON gene (MSTIR) maps to 3p21.3, a region frequently altered in lung cancer and other malignancies. It encodes a receptor tyrosine kinase (RTK) closely related to MET, whose mutations are associated with neoplasia. We investigated whether RON might be involved in the development or progression of lung cancer. We first determined the exon-intron structure of the gene by direct sequencing of RON cosmid DNA and PCR products containing intronic sequences, and then developed primers suitable for mutation analysis by the single-strand conformation polymorphism (SSCP) method. Twenty coding exons were characterized, ail but the first one small (average size: 170 bp), a feature shared with other RTK genes. We performed SSCP analysis of RON in small and non-small cell lung cancer samples, upon detection of its expression in a sample of lung cancer cell lines. A mutation (T915C: L296P) was found in an adenocarcinoma specimen. Several single nucleotide polymorphisms were also found. The panel of intron-anchored primers developed in this work will be useful for mutation analysis of the RON gene in different types of human tumors. (C) 2000 Wiley-Liss, Inc. [References: 40]

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