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Two target regions of allelic loss on chromosome 9 in urinary-bladder cancer
1Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki.
Abstract:
Allelic losses on chromosome 9 are common in a wide variety of human tumors; moreover, two predisposing loci for some inherited cancer syndromes, i.e., familial malignant melanoma and Gorlin syndrome, have been identified on this chromosome. To define the location of putative tumor suppressor genes involved in cancer of the urinary bladder, 85 bladder cancers were examined for allelic loss at 18 microsatellite loci on chromosome 9. Correlations were also sought between loss of heterozygosity on chromosome 9 and several clinicopathological parameters. Allelic loss was observed in 54 of the tumors (64%) and deletion mapping identified two target regions; one at an interval on 9p21 flanked by D9S736 and D9S165, and the other at an interval on 9q31-34 flanked by D9S58 and D9S61. No subtle mutation was detected in the PTCH gene which lies in the latter interval. Allelic loss on chromosome 9 was observed frequently in low grade and non-invasive tumors as well as in tumors of more advanced phenotype. Inactivation of tumor suppressor genes lying in either of two regions of common deletion identified on chromosome 9 might affect carcinogenic mechanisms at an early stage of tumor development in the urinary bladder.
Insights
Loss of genetic material on chromosome 9 is frequent in bladder cancers. This study identified two key regions on chromosome 9 associated with tumor suppressor genes, suggesting early involvement in bladder cancer development.
Area of Science:
- Oncology
- Genetics
- Urology
Background:
- Allelic losses on chromosome 9 are prevalent across various human cancers.
- Chromosome 9 harbors predisposing loci for inherited cancer syndromes like familial malignant melanoma and Gorlin syndrome.
- Understanding tumor suppressor genes on chromosome 9 is crucial for bladder cancer research.
Purpose of the Study:
- To pinpoint the location of potential tumor suppressor genes involved in urinary bladder cancer.
- To investigate the frequency and patterns of allelic loss on chromosome 9 in bladder tumors.
- To correlate chromosomal alterations with clinicopathological features of bladder cancer.
Main Methods:
- Analysis of allelic loss at 18 microsatellite loci on chromosome 9 in 85 bladder cancer samples.
- Deletion mapping to identify specific regions of chromosomal loss.
- Examination of the PTCH gene for mutations within a deletion region.
- Correlation of loss of heterozygosity with clinicopathological parameters.
Main Results:
- Allelic loss on chromosome 9 was detected in 64% (54 out of 85) of bladder tumors analyzed.
- Two critical regions of deletion were identified: one on 9p21 (between D9S736 and D9S165) and another on 9q31-34 (between D9S58 and D9S61).
- No mutations were found in the PTCH gene located in the 9q deletion region.
- Frequent allelic loss was observed across tumors of varying grades and invasiveness.
Conclusions:
- Inactivation of tumor suppressor genes in the identified chromosome 9 regions likely plays a role in early bladder cancer development.
- These findings highlight chromosome 9 as a significant site for genetic alterations in urinary bladder carcinogenesis.
- Further investigation into these regions may reveal novel therapeutic targets for bladder cancer.