Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
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.
Steck
P A
PA
Department of Neuro-Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. steckpa@audumla.mdacc.tmc.edu
Pershouse
M A
MA
Jasser
S A
SA
Yung
W K
WK
Lin
H
H
Ligon
A H
AH
Langford
L A
LA
Baumgard
M L
ML
Hattier
T
T
Davis
T
T
Frye
C
C
Hu
R
R
Swedlund
B
B
Teng
D H
DH
Tavtigian
S V
SV
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
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