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Distinct regions of allelic loss on chromosome 4 in human primary bladder carcinoma
T J Polascik1, P Cairns, W Y Chang
1James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Abstract:
Accumulating evidence implicates the presence of putative tumor suppressor genes on human chromosome 4 that are potentially inactivated in the genesis of several different neoplasms. To accurately determine the frequency of allelic loss on both arms of human chromosome 4, we screened 282 fresh-frozen human bladder carcinomas for allelic loss. Loss of heterozygosity of at least one marker for chromosome 4 was identified in 129 tumors (45.7%). Fine mapping was accomplished using up to 15 polymorphic markers on the p arm and 19 markers on the q arm. We identified a 3-cM minimal area of loss on the p arm between microsatellite markers D4S1608 and D4S404 deleted in 82 tumors (29%). A total of 68 tumors (24%) targeted a 14-cM critical region identified on the distal q arm between markers D4S426 and D4S408. Loss of these two regions correlated with advanced stage and grade of the lesions. These data identify distinct regions of loss on chromosome 4 potentially involved in the late progression of bladder carcinoma.
Insights
Researchers identified specific regions on chromosome 4 that are frequently lost in bladder cancer. These losses correlate with advanced tumor stage and grade, suggesting their role in cancer progression.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Human chromosome 4 harbors potential tumor suppressor genes implicated in various neoplasms.
- Inactivation of these genes is suspected in the development of several cancers.
Purpose of the Study:
- To determine the frequency of allelic loss on both arms of human chromosome 4 in bladder carcinomas.
- To identify specific regions of chromosomal loss associated with bladder cancer progression.
Main Methods:
- Screening of 282 fresh-frozen human bladder carcinomas for allelic loss using polymorphic markers.
- Fine mapping of chromosome 4p and 4q using 15 and 19 microsatellite markers, respectively.
Main Results:
- Loss of heterozygosity for chromosome 4 markers was observed in 45.7% of tumors.
- A minimal region of loss on chromosome 4p (D4S1608-D4S404) was deleted in 29% of tumors.
- A critical region on the distal chromosome 4q (D4S426-D4S408) was targeted in 24% of tumors.
- Loss in these regions correlated with advanced tumor stage and grade.
Conclusions:
- Distinct regions of loss on chromosome 4 are identified in bladder carcinomas.
- These chromosomal losses are potentially involved in the late-stage progression of bladder cancer.