title: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
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.
authors.affiliation: Department of Neuro-Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. steckpa@audumla.mdacc.tmc.edu
authors.forename: P A
authors.initials: PA
authors.lastname: Steck
authors.forename: M A
authors.initials: MA
authors.lastname: Pershouse
authors.forename: S A
authors.initials: SA
authors.lastname: Jasser
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: A H
authors.initials: AH
authors.lastname: Ligon
authors.forename: L A
authors.initials: LA
authors.lastname: Langford
authors.forename: M L
authors.initials: ML
authors.lastname: Baumgard
authors.forename: T
authors.initials: T
authors.lastname: Hattier
authors.forename: T
authors.initials: T
authors.lastname: Davis
authors.forename: C
authors.initials: C
authors.lastname: Frye
authors.forename: R
authors.initials: R
authors.lastname: Hu
authors.forename: B
authors.initials: B
authors.lastname: Swedlund
authors.forename: D H
authors.initials: DH
authors.lastname: Teng
authors.forename: S V
authors.initials: SV
authors.lastname: Tavtigian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human