Document Detail

Activating mutations of Gsalpha in kidney cancer.
MedLine Citation:
PMID:  16890646     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Heterotrimeric G proteins are signal transduction proteins coupled to hormone receptors that activate intracellular second messenger systems, mainly cyclic adenosine monophosphate mediated protein kinase. Recent studies indicate that G proteins may have a major role in oncogenesis as well as in tumor invasiveness and cell proliferation. The involvement of G proteins was formerly thought to be limited to hormonal signal transduction. Activating Gsalpha mutations have been reported in tumors arising only from highly specialized endocrine tissue, such as pituitary adenomas, toxic thyroid adenomas and differentiated thyroid carcinomas, but never in other nonendocrine tumors. We hypothesized that a constitutive activation of this pathway, that is activated Gsalpha and inhibited Gialpha, could be implicated in kidney cancers. We searched for alterations on the Gsalpha gene GNAS and the Gialpha gene in renal cell carcinoma. MATERIALS AND METHODS: Using nested polymerase chain reaction, enzyme digestions, laser microdissection and direct sequencing we looked for activating mutations on GNAS codons 201 and 227, and inhibiting mutations on the Gialpha gene in 30 consecutive patients with clear cell renal cell carcinoma between January 2003 and January 2004. RESULTS: Somatic (tumor specific) activating mutations of Gsalpha were present in a significant proportion of human clear cell renal cell carcinomas. Activating mutations were identified in 5 of the 30 patient DNA preparations (16.6%) with a substitution of arginine 201 by cysteine in 3 and histidine in 2. CONCLUSIONS: These findings suggest the implication of this pathway in human oncogenesis. It may provide a potential therapeutic approach to these frequent and aggressive tumors.
Nicolas Kalfa; Serge Lumbroso; Nathalie Boulle; Jacques Guiter; Laurent Soustelle; Pierre Costa; Heliette Chapuis; Pierre Baldet; Charles Sultan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of urology     Volume:  176     ISSN:  0022-5347     ISO Abbreviation:  J. Urol.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-07     Completed Date:  2006-09-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  891-5     Citation Subset:  AIM; IM    
INSERM U540, Endocrinologie Moléculaire et Cellulaire des Cancers and Service d'Hormonologie du Développement et de la Reproduction, Hôpital Lapeyronie, CHU Montpellier, 34295 Montpellier, France.
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MeSH Terms
Carcinoma, Renal Cell / genetics*
GTP-Binding Protein alpha Subunits, Gs / genetics*
Kidney Neoplasms / genetics*
Middle Aged
Reg. No./Substance:
EC Protein alpha Subunits, Gs

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