Alterations of Fas (APO-1/CD95) gene in transitional cell carcinomas of urinary bladder

Citation
Sh. Lee et al., Alterations of Fas (APO-1/CD95) gene in transitional cell carcinomas of urinary bladder, CANCER RES, 59(13), 1999, pp. 3068-3072
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
59
Issue
13
Year of publication
1999
Pages
3068 - 3072
Database
ISI
SICI code
0008-5472(19990701)59:13<3068:AOF(GI>2.0.ZU;2-9
Abstract
Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signalin g. The key role of the Fas system in negative growth regulation has been st udied mostly within the immune system, and somatic mutations of Fas in cant er patients have been described solely in lymphoid-lineage malignancies. We analyzed somatic mutations and loss of heterozygosity of Fas gene in 43 tr ansitional cell carcinomas of urinary bladder. Overall, 12 tumors (28%) wer e found to have Fns mutations, including 11 missense mutations and 1 frames hift mutation. Ten of the 12 mutations were located in the death domain kno wn to be involved in the transduction of an apoptotic signal, and 8 of thes e 10 mutations showed an identical G to A transition at bp 993, indicating a potential hotspot in bladder cancers. Three of eight (38%) informative tu mors 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 l ead to the loss of its apoptotic function and contribute to the pathogenesi s of some bladder cancers.