Classification of KIT/PDGFRA wild-type gastrointestinal stromal tumors: implications for therapy.
Expert Rev Anticancer Ther
; 15(6): 623-8, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25831232
ABSTRACT
Gastrointestinal stromal tumors (GIST) are driven mostly by oncogenic KIT or PDGFRA mutations. However, in 10-15% of all GIST, no such activating mutations can be found and these tumors are classified as 'wild-type GIST' (KIT/PDGFRA wt-GIST). Subgroups of KIT/PDGFRA wt-GIST are driven by other sporadic mutations involving the RAS/RAF/MAP-kinase pathway, such as BRAF or KRAS mutations. Furthermore, KIT/PDGFRA wt-GIST are observed in the context of hereditary syndromes, such as neurofibromatosis Type 1, in which the lack of neurofibromin 1 also leads to the activation of the RAS/RAF/MAP-kinase pathway. Finally, the deficiency succinate dehydrogenase seems to play a major role in KIT/PDGFRA wt-GIST. In conclusion, KIT/PDGFRA wt-GIST belong to different subgroups defined by diverse underlying genetic alterations leading to different biological phenotypes. The vast majority of KIT/PDGFRA wt-GIST will not respond to imatinib. Further research to unravel the pathogenesis of KIT/PDGFRA wt-GIST is prerequisite to the development of effective treatment strategies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-kit
/
Receptor alfa de Fator de Crescimento Derivado de Plaquetas
/
Tumores do Estroma Gastrointestinal
Limite:
Humans
Idioma:
En
Revista:
Expert Rev Anticancer Ther
Assunto da revista:
NEOPLASIAS
/
TERAPEUTICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha