p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features

Tetsuya Mitsudomi, Seth M. Steinberg, Marion M. Nau, David Carbone, Domenico D'Amico, Sara Bodner, Herbert K. Oie, R. Ilona Linnoila, James L. Mulshine, John D. Minna, Adi F. Gazdar

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Abstract

We screened 77 non-small-cell lung cancer (NSCLC) cell lines for mutations of the p53 gene using a single-strand conformation polymorphism (SSCP) assay. We found that 57 cell lines (74%) had mutations of the p53 gene. Three cell lines had a deletion of the p53 gene. Of the remaining 54 cell lines, 49 cell lines were sequenced and 52 mutations were confirmed. In contrast to previously published p53 mutations in other human tumors, the p53 gene mutations in NSCLC were diverse with regard to the location and nature of the mutations. The region corresponding to codons 144-166, which is outside the evolutionarily conserved regions, was a frequent site of p53 gene mutations in NSCLC. The presence of a p53 gene mutation was not associated with age, sex, histological types, culture site, treatment intent, presence of prior cytotoxic treatment, neuroendocrine differentiation, median culture time or patient survival. The prevalence of p53 mutations in cell lines with ras mutations did not differ from that in cell lines without ras mutations. However, p53 gene mutations in NSCLC cell lines with ras mutations tended to cluster in exon 8, suggesting the presence of a functional domain of the p53 gene relating to interaction with the ras gene. We conclude that p53 and ras mutations are frequent and apparently independent genetic alterations which play different roles in the pathogenesis, progression and prognosis of NSCLC.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalOncogene
Volume7
Issue number1
StatePublished - Jan 1992

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p53 Genes
Non-Small Cell Lung Carcinoma
Cell Line
Mutation
ras Genes
Codon
Exons

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. / Mitsudomi, Tetsuya; Steinberg, Seth M.; Nau, Marion M.; Carbone, David; D'Amico, Domenico; Bodner, Sara; Oie, Herbert K.; Linnoila, R. Ilona; Mulshine, James L.; Minna, John D.; Gazdar, Adi F.

In: Oncogene, Vol. 7, No. 1, 01.1992, p. 171-180.

Research output: Contribution to journalArticle

Mitsudomi, T, Steinberg, SM, Nau, MM, Carbone, D, D'Amico, D, Bodner, S, Oie, HK, Linnoila, RI, Mulshine, JL, Minna, JD & Gazdar, AF 1992, 'p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features', Oncogene, vol. 7, no. 1, pp. 171-180.
Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner S et al. p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene. 1992 Jan;7(1):171-180.
Mitsudomi, Tetsuya ; Steinberg, Seth M. ; Nau, Marion M. ; Carbone, David ; D'Amico, Domenico ; Bodner, Sara ; Oie, Herbert K. ; Linnoila, R. Ilona ; Mulshine, James L. ; Minna, John D. ; Gazdar, Adi F. / p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. In: Oncogene. 1992 ; Vol. 7, No. 1. pp. 171-180.
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