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[Cancer Research 59, 3068-3072, July 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 3068-3072, July 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

Alterations of Fas (APO-1/CD95) Gene in Transitional Cell Carcinomas of Urinary Bladder1

Sug Hyung Lee2, Min Sun Shin2, Won Sang Park, Su Young Kim, Seung Myung Dong, Jae Ho Pi, Hun Kyung Lee, Ho Sik Kim, Ja June Jang, Choo Soung Kim, Sang Ho Kim, Jung Young Lee and Nam Jin Yoo3

Departments of Pathology [S. H. L., M. S. S., W. S. P., S. Y. K., S. M. D., J. H. P., H. K. L., C. S. K., S. H. K., J. Y. L., N. J. Y.] and Biochemistry [H. S. K.], and Cancer Research Institute [S. H. L., W. S. P., J. Y. L., N. J. Y.], College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea, and Department of Pathology and Cancer Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea [J. J. J.]

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling. The key role of the Fas system in negative growth regulation has been studied mostly within the immune system, and somatic mutations of Fas in cancer patients have been described solely in lymphoid-lineage malignancies. We analyzed somatic mutations and loss of heterozygosity of Fas gene in 43 transitional cell carcinomas of urinary bladder. Overall, 12 tumors (28%) were found to have Fas mutations, including 11 missense mutations and 1 frameshift mutation. Ten of the 12 mutations were located in the death domain known to be involved in the transduction of an apoptotic signal, and 8 of these 10 mutations showed an identical G to A transition at bp 993, indicating a potential hotspot in bladder cancers. Three of eight (38%) informative tumors carrying Fas mutations showed LOH at polymorphic sites in the promoter region. This is the first report on the Fas gene mutations in nonlymphoid malignancies, and our data suggest that alterations of the Fas gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some bladder cancers.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.