02 per million children below the age of 14 years, which appears to be the most accurate epidemiological data to date on pediatric GIST (49). Pediatric GISTs are considered a rare entity that can be quite different from its adult counterpart and seen predominantly in the second decade (46,50,51) with a predilection for female patients (46). Sporadic

GISTs are most common and familial GISTs with germline mutation of the KIT gene are rare, but Inhibitors,research,lifescience,medical have been well described (52-55). These patients usually have multiple GISTs and cutaneous hyperpigmentation (53). In addition, GIST rarely occurs in association with other syndromes such as neurofibromatosis type I (56-59) or Carney’s triad, a nonfamilial condition with gastric GIST, paraganglioma, and pulmonary chondroma (60,61). The latter should be distinguished from Carney-Stratakis syndrome, an inherited tumor syndrome comprising gastric GIST and paragangliomas (62). GIST

co-existing with other tumors has been reported mainly as case report (63) and mostly with colorectal carcinomas or adenomas, Inhibitors,research,lifescience,medical followed by gastric carcinomas (64,65). p53, one of the most common involved genes in colorectal carcinogenesis, has also been found to have a prognostic significance in GISTs, and mutations in this tumor suppressor gene are more often observed in the high-risk GISTs (66). GIST colliding with other tumors, mostly gastric adenocarcinomas, Inhibitors,research,lifescience,medical is rarely seen in literature (67-69). Only one case of gastric GIST colliding with

angiosarcoma was reported (70). Pathogenesis and genetics In 1995 Huizinga and colleagues reported a knockout mice model of KIT failed to express in interstitial cells of Cajal cells (17). Inhibitors,research,lifescience,medical This finding led to the hypothesis that KIT was essential for the development of interstitial cells of Cajal cells. In 1998, Hirota and colleagues published a groundbreaking discovery of KIT mutations in GISTs (21) and 95% Inhibitors,research,lifescience,medical GISTs are immunohistochemically positive for the receptor tyrosine kinase KIT (also known as CD117) (21,22). It is now established that KIT mutations, which cause the constitutive activation of the kinase, are found in 70-80% of GISTs. CD117 becomes a crucial diagnostic marker for GIST, and mutant KIT provides an important therapeutic target clinically in GIST treatment. Initially, GISTs lacking any selleck products evidence of KIT mutation were classified as “wild type” (WT). In 2003, novel mutations in PDGFRA were found in WT GIST by Heinrich and colleagues (28). Currently PDGFRA mutations account for 5-10% of known mutations in GIST. from About 9-15% of all GISTs do not exhibit mutations in either KIT or PDGFRA and are now termed “wild type” (WT) (71). KIT is a member of the type III transmembrane receptor tyrosine kinase (RTK) family that includes PDGFRA and PDGFRB, as well as macrophage colony-stimulating-factor receptor (CSF1R) and Fl cytokine receptor (FLT1) (72). Normally, binding of the KIT ligand, stem cell factor (SCF) to KIT results in receptor dimerization and kinase activation (73).