Mutational analysis of the c-KIT AND PDGFRalpha in a series of molecularly well-characterized synovial sarcomas.
Diagn Mol Pathol
; 14(3): 134-9, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16106193
ABSTRACT
The c-KIT and the platelet-derived growth factor receptor alpha (PDGFRalpha) have been shown to be important for tumor growth and progression in several soft-tissue sarcomas, including synovial sarcomas (SSs). It has been suggested that these c-KIT-positive cases might benefit from a tyrosine kinase inhibitor therapy. In this study, we analyze a series of SSs to investigate the presence of c-KIT and PDGFRalpha mutations with the aim of selecting those for a more adequate and appropriate therapy. We analyzed fresh-frozen tissues from 12 SSs (8 primary tumors and 4 nude mice xenotransplants from primary tumors). RNA was extracted to identify the presence of the SYT-SSX gene fusion to confirm the SS diagnosis. Mutational analysis of exons 9, 11, 13, and 17 of c-KIT and exons 12 and 18 of PDGFRalpha was performed by direct sequencing. Immunohistochemical analysis of c-KIT, PDGFRalpha, and p-PDGFRalpha was also performed. All analyzed cases showed the presence of SYT-SSX gene fusion transcripts confirming the diagnosis of SS, 10 carried the SYT-SSX1 fusion, and 2 the SYT-SSX2. Immunohistochemical analysis showed expression of c-KIT in 3 cases in which no molecular alterations were detected. For the PDGFRalpha, we observed an in-frame deletion of codons 554 and 555 in a case which also showed a strong immunopositivity for the phosphorylated form of PDGFRalpha. PDGFRalpha expression was observed in 8 cases. We suggest that a more exhaustive mutational analysis of the c-KIT and PDGFRalpha genes should be performed to ascertain which cases would really benefit from a tyrosine kinase inhibitor therapy in SS.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Análise Mutacional de DNA
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Sarcoma Sinovial
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Proteínas Proto-Oncogênicas c-kit
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Receptor alfa de Fator de Crescimento Derivado de Plaquetas
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article