Nature Genetics
15, 356 - 362 (1997)
doi:10.1038/ng0497-356
Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancersPeter A. Steck1, 4, Mark A. Pershouse1, Samar A. Jasser1, W.K. Alfred Yung1, Huai Lin1, Azra H. Ligon1, Lauren A. Langford2, Michelle L. Baumgard3, Thomas Hattier3, Thaylon Davis3, Cheryl Frye3, Rong Hu3, Bradley Swedlund3, David H.R. Teng3
& Sean V. Tavtigian3
1Department of Neuro-Oncology, The Brain Tumour Center, University of Texas, M.D. Anderson Cancer Center, 1515Holcombe Boulevard, Houston Texas 77030, USA.
2Department of Pathology, The Brain Tumour Center, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston Texas 77030, USA.
3Myriad Genetics Inc. 390 Wakara Way, Salt Lake City, Utah 84108, USA.
4email: steckpa@audumla.mdacc.tmc.edu. 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.
REFERENCES
- Louis, D.N. & Gusella, J.F. A tiger behind many doors: multiple genetic pathways to malignant glioma. Trends. Genet. 11, 412−415 (1995). | Article | PubMed | ISI | ChemPort |
- Fults, D., Redone, C.A., Thomas, G.A. & White, R. Allelotype of human malignant astrocytoma. Cancer Res. 50, 5784−5789 (1990). | PubMed | ISI | ChemPort |
- Rahseed, B.K., Fuller, G.N., Friedman, A.M., Signer, D.D. & Signer, S.H. Loss of heterozygosity for 10q loci in human gliomas. Genes Chromosome Cancer 5, 75−82 (1992).
- Herbst, R.A., Weiss, J., Ehnis, A., Cavenee, W.K. & Arden, K.C. Loss of heterozygosity for 10q22-qter in malignant melanoma progression. Cancer Res. 54, 3111−3114 (1994). | PubMed | ISI | ChemPort |
- Rempel, S.A., Schwechheimer, K., Davis, R.L., Cavenee, W.K. & Rosenblum, M.L. Loss of heterozygosity for loci on chromosome 10 is associated with morphologically malignant meningioma progression. Cancer Res. 53, 2386−2392 (1993). | PubMed | ISI | ChemPort |
- Morita, R. et al. Common regions of deletion on chromosomes 5q, 6q, and 10q in renal cell carcinoma. Cancer Res. 51, 5817−5820 (1991). | PubMed | ISI | ChemPort |
- Eagle, L.R. et al. Mutation of the MX11 gene in prostate cancer. Nature Genet. 9, 249−255 (1995). | Article | PubMed | ISI | ChemPort |
- Peterson, I. et al. Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q, and 17p. Brit. J. Cancer 75, 79−86 (1997). | PubMed |
- Peiffer, S.L. et al. Allelic loss of sequences from the long arm of chromosome 10 and replication errors in endometrial cancers. Cancer Res. 55, 1922−1926 (1995). | PubMed | ISI | ChemPort |
- Gray, I.C. et al. Loss of chromosomal region 10q23-25 in prostate cancer. Cancer Res. 55, 4800−4803 (1995). | PubMed | ISI | ChemPort |
- Trybus, T.M., Burgress, A.C., Wojno, K.J., Glover, T.W. & Macoska, J.A. Distinct areas of allelic loss on chromosomal regions 10p and 10q in human prostate cancer. Cancer Res. 56, 2263−2267 (1996). | PubMed | ISI | ChemPort |
- Ransom, D.T. et al. Correlation of cytogenetic analysis and loss of heterozygosity studies in diffuse astrocytomas and mixed oligo-astrocytomas. Genes Chromosome. Cancer 5, 357−374 (1992). | ISI | ChemPort |
- Pershouse, M.A. et al. Analysis of the functional role of chromosome 10 loss in human glioblastomas. Cancer Res. 53, 5043−5050 (1993). | PubMed | ISI | ChemPort |
- Steck, P.A., Hadi, A., Cheong, H.C., Yung, W.K.A. & Pershouse, M.A. Evidence for two tumour suppressive loci on chromosome 10 involved in glioblastomas. Genes Chromosome. Cancer 12, 255−261 (1995). | ISI | ChemPort |
- Church, D.M. et al. Isolation of genes from complex sources of mammalian genomic DNA using exon amplification. Nature Genet. 6, 98−105 (1994). | Article | PubMed | ISI | ChemPort |
- Tavtigian, S.V. et al. The complete BCRA2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet. 12, 333−337 (1996). | Article | PubMed | ISI | ChemPort |
- Kozak, M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125−8148 (1987). | PubMed | ISI | ChemPort |
- Denu, J., Stuckey, J.A., Saper, D. & Dixon, J.E. Form and function in protein dephosphorylation. Cell 87, 361−364 (1996). | Article | PubMed | ISI | ChemPort |
- Denu, J.M. & Dixon, J.E. A catalytic mechanism for the dual-specific phosphatase. Proc. Natl. Acad. Sci. USA 92, 5910−5914 (1995). | PubMed | ChemPort |
- Spruck, C.H. et al. p16 gene in uncultured tumours. Nature 370, 183−184 (1994). | Article | PubMed | ISI |
- Herman, J.G. et al. Inactivation of the 2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 55, 4520−4530 (1995). | PubMed |
- Chou, P.Y. & Fassman-Fasman, G.D. Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from protein. Biochemistry 13, 211−222 (1974). | PubMed | ISI | ChemPort |
- von Diemling, A. et al. Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J. Neurosurg. 77, 295−301 (1992). | PubMed |
- Tokiyoshi, K., Yoshimine, T., Maruno, M., Muhammad, A.K.M.G. & Hayakawa, T. Accumulation of allelic losses on chromosome 10 in human gliomas at recurrence. J. Clin. Pathol:Mol. Pathol. 49, 218−222 (1996).
- Nihei, N. et al. Localization of a metastasis suppressor gene(s) for rat prostatic cancer to the long arm of human chromosome 10. Genes Chromosome. Cancer 14, 112−119 (1995). | ISI | ChemPort |
- Albarosa, A., DiDonato, S. & Finocchiaro, G. Redefinition of the coding sequence of the MXI-1 gene and identification of a polymorphic repeat in the 3' non-coding region that allows the detection of loss of heterozygosity of chromosome 10q25 in glioblastomas. Hum. Genet. 95, 709−711 (1995). | PubMed | ISI | ChemPort |
- Nelen, M.R. et al. Localization of the gene for Cowdens disease to 10q22-23. Nature Genet. 13, 114−116 (1996). | Article | PubMed | ISI | ChemPort |
- Eng, C. et al. Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? J. Med. Genet. 31, 458−461 (1994). | PubMed | ISI | ChemPort |
- Teng, D.H.-F. et al. Low incidence of BRAC2 mutation in breast carcinoma and other cancers. Nature Genet. 13, 241−248 (1996). | Article | PubMed | ISI | ChemPort |
- Barford, D., Flint, A.J. & Tonks, N.K. Crystal structure of human protein tyrosine phosphatase 1b. Science 263, 1397−1404 (1994). | PubMed | ISI | ChemPort |
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