Mutational analysis of N-ras, p53, p16INK4a, p14ARF and CDK4 genes in primary human malignant mesotheliomas

Int J Oncol. 2001 Feb;18(2):425-33. doi: 10.3892/ijo.18.2.425.


Nineteen specimens from primary human malignant mesotheliomas obtained from 19 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 by combined RFLP-PCR/SSCP analysis. In addition, all tumours were screened for deletions and point mutations in the tumour suppressor genes p53, p16INK4a (CDKN2A) and p14ARF (exon-1beta) by combined multiplex-PCR/SSCP analysis. No mutations were found in N-ras, p53 and CDK4. Three tumours displayed homozygous deletion (co-deletion of exons 1, 2 and 3) of p16INK4a. One of them displayed additional homozygous deletion of p14ARF (exon-1beta). Two silent point mutations and 2 polymorphisms were found in p16INK4a in 3 tumours. Our preliminary data indicate that disarrangement of the Rb1 pathway may be involved in mesothelioma formation.

MeSH terms

  • Adult
  • Aged
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / genetics*
  • DNA Mutational Analysis
  • Female
  • Gene Frequency / genetics
  • Genes, p16 / genetics*
  • Genes, p53 / genetics*
  • Genes, ras / genetics*
  • Humans
  • Loss of Heterozygosity / genetics
  • Male
  • Middle Aged
  • Neoplasms, Mesothelial / genetics*
  • Point Mutation / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Proto-Oncogene Proteins*
  • Tumor Cells, Cultured / physiology
  • Tumor Suppressor Protein p14ARF


  • Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p14ARF
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases