Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines

Oncogene. 1998 Jan 8;16(1):89-93. doi: 10.1038/sj.onc.1201512.


Loss of heterozygosity (LOH) at chromosome 10q23-q25 is frequent in small cell lung cancer (SCLC), indicating the presence of putative tumor suppressor genes. PTEN/ MMAC1, a newly cloned candidate tumor suppressor gene at 10q23, was mutated in multiple human cancers. We investigated whether mutations of PTEN/MMAC1 play an important role in SCLC tumorigenesis. We examined 16 SCLC cell lines for PTEN/MMAC1 mRNA expression by reverse-transcriptase polymerase chain reaction (RT-PCR) and potential mutations by sequencing analysis of the PTEN/MMAC1 coding region. No mutation was observed in PTEN/MMAC1 cDNAs in 15 cell lines expressing PTEN/MMAC1. One SCLC cell line, DMS79, did not have detectable PTEN/ MMAC1 expression. Importantly, we identified a novel homologue of PTEN/MMAC1, termed PTH2, localized to chromosome 9p21-q13 and containing only ten amino acid substitutions compared with the PTEN/MMAC1 coding region. However, because the putative initiation codon for PTEN/MMAC1 gene was changed to arginine in PTH2, the translational initiation site of PTH2 is very likely to differ from that of the PTEN/MMAC1. PTH2 was expressed in two normal lung tissues and two normal colon tissues, but in only four of 16 SCLC cell lines. A missense mutation in PTH2 was identified in a SCLC cell line that did not express PTEN/MMAC1 mRNA. Our data suggest that inactivation of PTEN/ MMAC1 is a rare event in SCLC tumorigenesis. However, the PTEN/MMAC1 homologue PTH2 may play a role in SCLC tumorigenesis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / pathology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 9
  • DNA, Complementary
  • Genes, Tumor Suppressor*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Molecular Sequence Data
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases*
  • Polymerase Chain Reaction
  • Protein Tyrosine Phosphatases / genetics*
  • Proteins / genetics*
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


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

Associated data

  • GENBANK/AF019083