Identification of a Candidate Tumour Suppressor Gene, MMAC1, at Chromosome 10q23.3 That Is Mutated in Multiple Advanced Cancers

Nat Genet. 1997 Apr;15(4):356-62. doi: 10.1038/ng0497-356.

Abstract

Deletions involving regions of chromosome 10 occur in the vast majority (> 90%) of human glioblastoma multiformes. A region at chromosome 10q23-24 was implicated to contain a tumour suppressor gene and the identification of homozygous deletions in four glioma cell lines further refined the location. We have identified a gene, designated MMAC1, that spans these deletions and encodes a widely expressed 5.5-kb mRNA. The predicted MMAC1 protein contains sequence motifs with significant homology to the catalytic domain of protein phosphatases and to the cytoskeletal proteins, tensin and auxilin. MMAC1 coding-region mutations were observed in a number of glioma, prostate, kidney and breast carcinoma cell lines or tumour specimens. Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Chromosomes, Human, Pair 10 / genetics*
  • DNA Mutational Analysis
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor / genetics*
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neoplasms / genetics
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases*
  • Protein Tyrosine Phosphatases / genetics*
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*

Substances

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

Associated data

  • GENBANK/U92435
  • GENBANK/U92436
  • GENBANK/U92437