GIST is a subset of GI mesenchymal tumors classified and diagnosed by advanced immunohistochemistry methods. GISTS are fairly rare tumors that are believed to originate in specialized cells in the intestinal wall. There are about 5,000 incidences of GIST in the US and up until the year 2000, no effective therapy existed for these types of GI neoplasms.
Two tyrosine kinase cell signaling proteins, c-KIT and PDGFR, play an active role in the pathogenic events leading to GIST, particularly when mediated by constitutively activated mutations. Imatinib, a targeted agent that inhibits both c-KIT and PDGFR, has been approved as front line therapy for GIST. GIST genotyping for C-KIT and PDGFR helps in confirming diagnosis and in guiding optimum dose of imatinib, as well as, prediction of response to second line therapies.1
As the table depicts below, the majority to GIST mutations are found in KIT exon 9 and 11. Overall mutation rate among GIST patients is 86%.2
| Mutation Location | Frequency | Aberrations |
|---|---|---|
| KIT exon 11 | 67% | 502AY503dup |
| KIT exon 9 | 10% | Deletions, insertions, point mutations |
| KIT exons 13 and 17 | 2% | K642E, Point Mutations |
| PDGFRA exons 12 and 14 | 1.4% | Deletions, Point Mutations |
| PDGFRA exon 18 | 6.1% | D842V |
| Wildtype | 14% |
MolecularMD has validated assays for analysis of Kit Exon 11 and 9 aberrations using RQ-PCR and direct sequencing and partners with Oregon Health & Science University to provide analysis of other rare mutations.
Click here for more information on our test menus.
1Corless et al, J Clin Oncol, 2004; 22:3813
2Heinrich MC, et al, ASCO 2006