These tumors are currently defined by having no mutations in exons 9, 11, 13, and 17 of the KIT gene and exons 12, 14, and 18 of the PDGFRA gene. Diagnosis
CT scanning is often undertaken (see the radiology section). The definitive diagnosis is made with a biopsy, which can be obtained endoscopically, percutaneously with CT or ultrasound guidance or at the time of surgery. A biopsy sample will be investigated under the microscope by a pathologist physician. The pathologist examines the histopathology to identify the characteristics of GISTs (spindle cells in 70-80%, epitheloid aspect in 20-30%). Smaller tumors can usually be confined to the muscularis propria layer of the intestinal wall. Large ones grow, mainly outward, from the bowel wall until the point where they outstrip their blood supply and necrose (die) on the inside, forming a cavity that may eventually come to communicate with the bowel lumen. When GIST is suspected—as opposed to other causes for similar tumors—the pathologist can use immunohistochemistry (specific antibodies that stain the molecule CD117 [also known as c-KIT] —see below). 95% of all GISTs are CD117-positive (other possible markers include CD34, DOG-1, desmin, and vimentin). Other cells that show CD117 positivity are mast cells. If the CD117 stain is negative and suspicion remains that the tumor is a GIST, the newer antibody DOG-1 (Discovered On GIST-1) can be used. Also, sequencing of KIT and PDGFRA can be used to prove the diagnosis. Imaging
The purpose of radiologic imaging is to locate the lesion, evaluate for signs of invasion and detect metastasis.
Mutations generally occur in the DNA encoding the intracellular part (exon 11), which acts as a tyrosine kinase to activate other enzymes. Mutations make c-KITfunction independent of activation by scf, leading to a high cell division rate and possibly genomic instability. Additional mutations are likely "required" for a cell with a c-KIT mutation to develop into a GIST, but the c-KIT mutation is probably the first step of this process. Mutations in the exons 11, 9 and rarely 13 and 17 of the c-KIT gene are known to occur in GIST. The tyrosine kinase function of c-KIT is important in the medical therapy for GISTs, as described below. KIT-D816V point mutations in c-KIT exon 17 are responsible for resistance to targeted therapy drugs like imatinib mesylate, a tyrosine kinase inhibitor. KIT-p.D419del (exon 8) — A subset of gastrointestinal stromal tumors previously regarded as wild-type tumors carries somatic activating mutations in KIT exon 8 (p.D419del). PDGFRA mutations
Most GIST cells with wildtype (i.e. not mutated) c-KIT instead have a mutation in another gene, PDGFR-α (platelet-derived growth factor receptor alpha), which is a related tyrosine kinase. Mutations in c-KIT and PDGFrA are mutually exclusive [4][5]. Wild-type tumors
Lesser numbers of GISTs appear to be associated with neither c-KIT nor PDGFR-α abnormalities. : 1062  About 10-15% of gastrointestinal stromal tumors (GISTs) carry wild-type sequences in all hot spots of KIT and platelet-derived growth factor receptor alpha (PDGFRA) (wt-GISTs).