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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
High frequency of chromosome 9p allelic loss and CDKN2 tumor suppressor gene alterations in squamous cell carcinoma of the bladder
Journal of the National Cancer Institute, Volume 87, No. 18, Year 1995
Notification
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Description
Background: In the Western Hemisphere, 90% of bladder cancers are transitional cell carcinomas, while only 7% are classified as squamous cell carcinomas. In contrast, in Egypt and regions of the Middle East and Africa, where infection by the trematode Schistosoma haematobium is endemic, squamous cell carcinoma is the most common bladder cancer as well as the most common cancer in men. Purpose: We planned experiments to understand the genetic defects underlying the development of squamous cell carcinoma and to determine if the morphologically and clinically distinct squamous cell carcinoma and transitional cell carcinoma of the bladder evolve following different genetic alterations. Methods: Squamous cell carcinoma specimens from high-risk (Egypt, n = 19) and low-risk (Sweden, n = 12) populations were examined for genetic defects known to be involved in transitional cell carcinoma tumorigenesis. Homozygous deletions of the CDKN2 tumor suppressor gene were detected by comparative multiplex polymerase chain reaction. Mutations in the CDKN2 and p53 (also known as TP53) genes were analyzed by single-strand conformation polymorphism and DNA sequencing. Immunohistochemical staining of p53 protein was also performed. Allelic losses in chromosome arms 9p, 9q, and 17p were determined by microsatellite analysis. Results: Homozygous deletions and sequence mutations in the CDKN2 gene were found in 67% (eight of 12) of squamous cell carcinoma specimens, a frequency three times higher than that reported for uncultured transitional cell carcinomas (P = .009). Hemizygous and homozygous deletions in 9p, where CDKN2 resides, were found in 92% (11 of 12) of uncultured squamous cell carcinomas, while only about 39% (35 of 90) of transitional cell carcinomas showed these losses (P = .001). Deletions in 9p with no change in 9q were found in 92% (10 of 11) of squamous cell carcinomas compared with only 10% (11 of 110) of transitional cell carcinomas (P<.001) reported in the literature. The frequency of p53 mutations in squamous cell carcinomas was similar to that reported for invasive transitional cell carcinomas (60%), but the type and position of mutations differed between the two tumor types. Allelic losses in chromosome arm 17p, where the p53 gene resides, were found to be less frequent in squamous cell carcinomas (38%) than in invasive transitional cell carcinomas (60%). Conclusions: Our results suggest that a putative tumor suppressor gene on 9p, possibly CDKN2, may contribute to squamous cell carcinoma tumorigenesis. Our data on squamous cell carcinoma and previously reported data on transitional cell carcinoma indicate that these two bladder carcinomas differ in their genetic alterations, suggesting that distinct underlying genetic defects may explain, at least in part, the pathological differences between the two tumors of the bladder epithelium. Implications: Development of diagnostic and therapeutic strategies for squamous cell carcinoma of the bladder based on its distinct genetic alterations is warranted. [J Natl Cancer Inst 1995;87:1383-93] © 1995 Oxford University Press.
Authors & Co-Authors
Gonzalez-zulueta, Mirella
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Shibata, Atsuko
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Ohneseit, Petra F.
Unknown
University of tü
Spruck, Charles H.I.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Busch, Christer
Unknown Affiliation
Shamaa, Moustafa A.
Egypt, Mansoura
Mansoura University, Urology and Nephrology Center
Elbaz, Mustafa
Egypt, Mansoura
Mansoura University, Urology and Nephrology Center
Nichols, Peter W.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Gonzalgo, Mark L.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Malmström, P. ‐U
Sweden, Uppsala
Uppsala Universitet
Jones, Peter A.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Statistics
Citations: 76
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1093/jnci/87.18.1383
ISSN:
00278874
Research Areas
Cancer
Genetics And Genomics
Study Locations
Egypt
Participants Gender
Male