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Inactivation of MMAC1 in bladder transitional-cell carcinoma cell lines and specimens
J Liu1, D C Babaian, M Liebert
1Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Abstract:
We recently limited the location of a candidate tumor suppressor gene in invasive (T3a/b) bladder transitional-cell carcinoma (TCC) to a 2.5-cM region at chromosome 10q23.3. This region harbors the MMAC1/PTEN/TEP1 gene (referred to hereafter as MMAC1), a dual-phosphatase tumor-suppressor gene frequently inactivated in variety of malignant tumors. In the present study, we examined whether MMAC1 is a target for inactivation by mutations and deletions in bladder TCC cell lines and specimens. MMAC1 was inactivated by homozygous deletions and mutations in three (27%) of 11 bladder cancer cell lines. One cell line, UC-3, had homozygous deletions, and two other cell lines, T-24 and UC-9, had missense mutations. T-24 had also a nonsense mutation. However, none of the 33 bladder TCC specimens examined had a mutation or deletion in the coding region. These results suggest that MMAC1 is not the primary target for inactivation in bladder TCC and that another gene, in close proximity to the MMAC1 locus, within this region of frequent allelic losses, may be the target for inactivation.
Insights
The MMAC1 gene, a candidate tumor suppressor, showed inactivation in bladder cancer cell lines but not in patient specimens. This suggests another nearby gene may be responsible for bladder transitional-cell carcinoma.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- A candidate tumor suppressor gene was localized to chromosome 10q23.3 in invasive bladder transitional-cell carcinoma (TCC).
- This region contains the MMAC1/PTEN/TEP1 gene (MMAC1), a dual-phosphatase tumor suppressor frequently inactivated in various cancers.
Purpose of the Study:
- To investigate if MMAC1 is inactivated by mutations or deletions in bladder TCC cell lines and specimens.
- To identify the specific tumor suppressor gene responsible for bladder TCC development.
Main Methods:
- Analysis of bladder cancer cell lines and patient tumor specimens.
- Detection of homozygous deletions and mutations within the MMAC1 gene coding region.
Main Results:
- MMAC1 inactivation via homozygous deletions and mutations was observed in 27% (3/11) of bladder cancer cell lines.
- One cell line (UC-3) exhibited homozygous deletions, while two (T-24, UC-9) had missense mutations; T-24 also had a nonsense mutation.
- No mutations or deletions in the MMAC1 coding region were found in 33 bladder TCC patient specimens.
Conclusions:
- MMAC1 is likely not the primary target for inactivation in bladder TCC.
- Another gene located near MMAC1 on chromosome 10q23.3, within a region of frequent allelic loss, may be the actual target gene in bladder TCC development.