Document Detail


Frequent Fas gene mutations in testicular germ cell tumors.
MedLine Citation:
PMID:  12163388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Fas (Apo-1/CD95)/Fas ligand (L) system is involved in cell death signaling, and has been suggested to be important for the regulation of germ cell apoptosis in the testis. Mutations of the Fas gene may result in accumulation of germ cells and thus might contribute to testicular carcinogenesis. The open reading frame of Fas cDNA was examined in 24 cases of testicular germ cell tumors (TGCTs), comprised of 19 pure histological type (15 seminomas, 3 embryonal carcinomas, 1 immature teratoma) and 5 mixed-type tumors. Mutations of the Fas gene were found in nine (37.5%) of these cases. Each lesion with a homogeneous histological picture was selectively microdissected using a laser capture microdissection method: samples consisted of 18 lesions from seminomas, 7 embryonal carcinomas, 4 immature teratomas, 2 choriocarcinomas, and 1 from a yolk sac tumor. Microdissected genomic DNA was examined to determine which mutations were derived from which kind of histological lesion. Eleven mutations were detected in 10 TGCT lesions from nine cases, but none were found in benign lesions. All were point mutations, and eight missense mutations occurred in exon 9 encoding the core protein of the death domain essential for apoptotic signal transduction. Three were silent mutations. Mutations were found in the seminoma (27.8%) and embryonal carcinoma lesions (62.5%), but none were found in the one yolk sac tumor, two choriocarcinomas, or four immature teratoma lesions. Each seminoma and embryonal carcinoma lesion found in the same case had a different type of Fas mutation from the others. Mouse T-cell lymphoma cells transfected with missense mutated genes were resistant to apoptosis induced by anti-Fas antibody, indicating these to be loss-of-function mutations. These findings suggested a role of Fas gene mutations in the pathogenesis of TGCTs.
Authors:
Hitoshi Takayama; Tetsuya Takakuwa; Yuichi Tsujimoto; Yoichi Tani; Norio Nonomura; Akihiko Okuyama; Shigekazu Nagata; Katsuyuki Aozasa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of pathology     Volume:  161     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-08-06     Completed Date:  2002-08-28     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  635-41     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Osaka University Medical School, Suita, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD95 / genetics*
Cell Death
Gene Frequency
Humans
Male
Middle Aged
Mutation*
Neoplasms, Germ Cell and Embryonal / genetics*,  pathology
Plasmids
Testicular Neoplasms / genetics*,  pathology
Chemical
Reg. No./Substance:
0/Antigens, CD95
Comments/Corrections

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