Mutation analysis of the PTEN/MMAC1 gene in lung cancer

Oncogene. 1998 Sep 24;17(12):1557-65. doi: 10.1038/sj.onc.1202070.


We studied PTEN/MMAC1, a newly discovered candidate tumor suppressor gene at 10q23.3, for mutations in lung cancer. One hundred and thirty-six lung cancer cell line DNAs (66 small cell lung cancers, SCLC, 61 non-small cell lung cancers, NSCLC, four mesotheliomas, five extrapulmonary small cell cancers) were analysed for PTEN/MMAC1 homozygous deletions and five (8%) SCLC lines showed homozygous deletions interrupting the PTEN/MMAC1 gene. Using single stranded conformation polymorphism (SSCP) analysis, we screened the PTEN/MMAC1 open reading frame of 53 lung cancer cell line cDNAs for point mutations and found that 3/35 SCLCs and 3/18 NSCLCs contained homozygous amino acid sequence altering mutations. Northern blot analysis revealed that expression of the PTEN/MMAC1 gene was considerably lower in all the tumor cell lines with point mutations while no expression was detected for cell lines with PTEN/MMAC1 homozygous deletions. Mutation analysis of 22 uncultured, microdissected, primary SCLC tumors and metastases showed two silent mutations, and two apparent homozygous deletions. We also discovered a processed pseudogene (PTEN2) which has 98.5% nt identity to PTEN/MMAC1, that needs to be accounted for in cDNA mutation analysis. Our findings suggest that genetic abnormalities of the PTEN/MMAC1 gene are only involved in a relatively small subset of lung cancers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / secondary
  • Chromosome Mapping
  • DNA Mutational Analysis
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Loss of Heterozygosity
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mutation*
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases*
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Protein Tyrosine Phosphatases / genetics*
  • Pseudogenes
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • Protein Tyrosine Phosphatases
  • PTEN Phosphohydrolase
  • PTEN protein, human