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Related Experiment Videos

p53 mutations in human lung tumors.

C W Miller1, K Simon, A Aslo

  • 1Department of Medicine, UCLA School of Medicine 90024.

Cancer Research
|April 1, 1992
PubMed
Summary

p53 gene mutations and loss of heterozygosity (LOH) are common in lung cancers, particularly small cell lung cancer. Tobacco smoke may cause G to T mutations in p53, a key tumor suppressor gene.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor suppressor gene p53 plays a critical role in preventing cancer.
  • Alterations in p53, including mutation and loss of heterozygosity (LOH), are frequent in various cancers, notably lung cancer.
  • Tobacco smoke is a known mutagenic agent implicated in lung cancer development.

Purpose of the Study:

  • To investigate the frequency and types of p53 gene mutations in lung cancer.
  • To determine the association between p53 mutations, LOH, and tobacco smoke exposure.
  • To identify the role of p53 alterations in the pathogenesis of small cell lung cancer.

Main Methods:

  • Direct sequencing of p53 exons 4-8 (mutational hotspots) in DNA from 40 lung cancer patients.
  • Preselection of samples for LOH in the p53 region.

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  • Analysis of mutation types, including G to T transversions and nonsense mutations.
  • Correlation of p53 alterations with LOH status and clinical data.

    • Main Results:

    • 23 distinct p53 mutations were identified in 22 of 40 lung cancer samples.
    • G to T transversions on the nontranscribed strand, consistent with tobacco smoke mutagenesis, accounted for half of the mutations.
    • p53 mutations were detected in 70% of small cell lung cancer samples.
    • Complete concordance was observed between p53 mutation and LOH in 18 samples.
    • Twelve samples with LOH showed no detectable p53 mutations, suggesting other genetic alterations.

    Conclusions:

    • p53 gene mutation is highly prevalent in small cell lung cancer.
    • Tobacco smoke is a likely contributor to p53 mutagenesis in lung cancer.
    • LOH in the p53 region is strongly associated with p53 mutation, but alternative tumor suppressor mechanisms may exist.