Mutations of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors

STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications

“…However, contemporary histopathological criteria, particularly expression of the c-KIT receptor tyrosine kinase (CD117), enable true non-myogenic GISTs to be discriminated from other gastrointestinal mesenchymal tumors (De Saint Aubain Somerhausen and Fletcher, 1998;SarlomoRikala et al, 1998;Chan, 1999;Miettinen et al, 1999;Rubin et al, 2000;Nishida and Hirota, 2000). Sequencing of the c-KIT gene has revealed activating mutations in many GISTs, and GISTs lacking c-KIT mutations may have a better prognosis Ernst et al, 1998;Moskaluk et al, 1999;Lasota et al, 1999;Taniguchi et al, 1999). A key role for c-KIT in GIST pathogenesis is supported by the ®nding that some kindreds with an autosomal dominant pattern of multiple primary GISTs have germline c-KIT activating mutations .…”

Improved Detection of KIT Exon 11 Duplications in Formalin-Fixed, Paraffin-Embedded Gastrointestinal Stromal Tumors

“…[1][2][3] A great majority of these mutations affects KIT juxtamembrane domain encoded by exon 11 and represent deletions and point mutations; however, insertions and duplications have also been reported. 4,5 Although most of the deletions and point mutations cluster in the 5Ј part, duplications have been found almost exclusively in the 3Ј part of KIT exon 11. 6,7 In addition, duplications are predominantly associated with gastric tumor location.…”

Apparent KIT Ser715 Deletion in GIST mRNA Is Not Detectable in Genomic DNA and Represents a Previously Known Splice Variant of KIT Transcript

“…Several studies have indicated a strong correlation between the existence of exon 11 mutations, a malignant phenotype and aggressive clinical behavior. [3][4][5][6][7][8][9] Our recent study demonstrated the occurrence of clinically highly malignant GIST lacking any KIT gene mutations as well as KIT mutation in a small incidentally detected GIST with an entirely benign histology and clinical course. These findings suggest that the relationship between KIT mutations and biological behavior is more complex than previously recognized.…”