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Gastrointestinal stromal tumor - an evolving concept.

Tornillo L - Front Med (Lausanne) (2014)

Bottom Line: The information on the mutational status of these tumors is essential to predict (and subsequently to plan) the therapy.As resistant cases are frequently wild type, other possible oncogenic events, defining other "entities," have been discovered (e.g., succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, and mutations in the RAS-RAF-MAPK pathway).The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University of Basel , Basel , Switzerland.

ABSTRACT
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases (RTKs) CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with RTK inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan) the therapy. As resistant cases are frequently wild type, other possible oncogenic events, defining other "entities," have been discovered (e.g., succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, and mutations in the RAS-RAF-MAPK pathway). The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

No MeSH data available.


Related in: MedlinePlus

Structure of RTK III, with localization of the activating mutations in KIT and PDGFRA. EC, extracellular; JM, juxtamembrane; TK, tyrosine kinase.
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Figure 2: Structure of RTK III, with localization of the activating mutations in KIT and PDGFRA. EC, extracellular; JM, juxtamembrane; TK, tyrosine kinase.

Mentions: CKIT and PDGFRA are RTK III, together with PDGFRB, macrophage colony-stimulating-factor receptor (CSFR1), FLT1, Flk/KDR, and Fl cytokine receptor (FLT3) (28, 29). RTK III have five Ig-like extracellular domains, one transmembrane domain, one intracellular juxtamembrane regulatory domain, and two intracellular tyrosine kinase domain with autophosphorylating capacity (29) (Figure 2). CKIT and PDGFRA are located on the same chromosomal region (4q12) and are very similar, both in the sequence and in the structure (29). The ligands (stem cell factor, SCF for CKIT and platelet-derived growth factor, PDGF for PDGFRA) cause homodymerization of the receptor. Subsequently, the TK domains autophosphorylate and activate, triggering the metabolic pathways of RAS-RAF-MAPK, PI3K-AKT, and signal transducer and activator of transcription 3 (STAT3) (30–34).


Gastrointestinal stromal tumor - an evolving concept.

Tornillo L - Front Med (Lausanne) (2014)

Structure of RTK III, with localization of the activating mutations in KIT and PDGFRA. EC, extracellular; JM, juxtamembrane; TK, tyrosine kinase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4291900&req=5

Figure 2: Structure of RTK III, with localization of the activating mutations in KIT and PDGFRA. EC, extracellular; JM, juxtamembrane; TK, tyrosine kinase.
Mentions: CKIT and PDGFRA are RTK III, together with PDGFRB, macrophage colony-stimulating-factor receptor (CSFR1), FLT1, Flk/KDR, and Fl cytokine receptor (FLT3) (28, 29). RTK III have five Ig-like extracellular domains, one transmembrane domain, one intracellular juxtamembrane regulatory domain, and two intracellular tyrosine kinase domain with autophosphorylating capacity (29) (Figure 2). CKIT and PDGFRA are located on the same chromosomal region (4q12) and are very similar, both in the sequence and in the structure (29). The ligands (stem cell factor, SCF for CKIT and platelet-derived growth factor, PDGF for PDGFRA) cause homodymerization of the receptor. Subsequently, the TK domains autophosphorylate and activate, triggering the metabolic pathways of RAS-RAF-MAPK, PI3K-AKT, and signal transducer and activator of transcription 3 (STAT3) (30–34).

Bottom Line: The information on the mutational status of these tumors is essential to predict (and subsequently to plan) the therapy.As resistant cases are frequently wild type, other possible oncogenic events, defining other "entities," have been discovered (e.g., succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, and mutations in the RAS-RAF-MAPK pathway).The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pathology, University of Basel , Basel , Switzerland.

ABSTRACT
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases (RTKs) CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with RTK inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan) the therapy. As resistant cases are frequently wild type, other possible oncogenic events, defining other "entities," have been discovered (e.g., succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, and mutations in the RAS-RAF-MAPK pathway). The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

No MeSH data available.


Related in: MedlinePlus