Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer

I. Chiba, T. Takahashi, M. M. Nau, D. D'Amico, D. T. Curiel, T. Mitsudomi, D. L. Buchhagen, D. Carbone, S. Piantadosi, H. Koga, P. T. Reissman, D. J. Slamon, E. C. Holmes, J. D. Minna

    Research output: Contribution to journalArticlepeer-review

    523 Scopus citations

    Abstract

    The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers. We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing. Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor specimens, but not in the corresponding normal lung, were distributed between codons 132 to 283, and included tumors with and without 17p allele loss. Fifteen of the 23 mutations lay in the predicted binding regions for SV40 large T antigen, and 14 were located in regions highly conserved between species. G to T transversions were a common result of p53 mutations in lung cancer compared to other cancers suggesting exposure to different mutagens. In univariate and multivariate analysis the presence of p53 mutations was associated with younger age and squamous histology. However, the presence of p53 mutations was not significantly associated with tumor stage, nodal status or sex and was found in all histologic types of lung cancer. We conclude that somatic mutations in the p53 gene play an important role in the pathogenesis of early stage non-small cell lung cancer.

    Original languageEnglish (US)
    Pages (from-to)1603-1610
    Number of pages8
    JournalOncogene
    Volume5
    Issue number10
    StatePublished - 1990

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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