Molecular analysis of the von Hippel-Lindau disease tumor suppressor gene in human lung cancer cell lines

Yoshitaka Sekido, Scott Bader, Farida Latif, James R. Gnarra, Adi F. Gazdar, W. Marston Linehan, Berton Zbar, Michael I. Lerman, John D. Minna

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

The deletion of the short arm of chromosome 3 is frequently observed in lung cancer. To determine whether the von Hippel-Lindau (VHL) disease tumor suppressor gene located at 3p25 is responsible for oncogenesis in lung cancer, we searched the known open reading frame using the single-strand conformation polymorphism (SSCP) technique for mutations in the VHL gene in 72 cancer cell lines including small cell (SCLC) and non-small cell (NSCLC) lung cancers, carcinoids, and mesotheliomas. SSCP analysis showed that four cell lines have altered SSCP patterns within the coding region and one in an intron of the VHL gene. SCLC line NCI-H1672 had a somatic mutation, G to A at nucleotide (nt) 530, leading to amino acid substitution (glycine to aspartic acid) compared to normal DNA from the same patient. Mesothelioma line NCI-H28 had T to A mutation at nt 479 leading to leucine to histidine amino acid change. We found one frequent polymorphism A (0.72) or G (0.28) at nt 19 resulting in either serine or glycine at this position, changes also found in normal peripheral blood cell DNA, often in a heterozygous state. In addition, we found single rare polymorphisms which did not alter the coding region including: C to G at nt 396, G to T at nt 843, and C to T change in an intron. These results suggest that the VHL gene is only rarely mutated in thoracic malignancies.

Original languageEnglish (US)
Pages (from-to)1599-1604
Number of pages6
JournalOncogene
Volume9
Issue number6
StatePublished - Jun 1 1994

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Sekido, Y., Bader, S., Latif, F., Gnarra, J. R., Gazdar, A. F., Linehan, W. M., Zbar, B., Lerman, M. I., & Minna, J. D. (1994). Molecular analysis of the von Hippel-Lindau disease tumor suppressor gene in human lung cancer cell lines. Oncogene, 9(6), 1599-1604.