What is the importance of KIT and PDGFRA genes in gastrointestinal stromal tumors (GIST) ?

KIT mutations which have a role for growth of tumor cells are determined approximately 80% in GIS tumor (GIST) cases. However, in some cases that KIT mutations are not determined, PDGFRA gene mutations are being observed (%5-7 of GISTs. Mutation localizations in the gene provide us previously whether patients will have a response or not for treatment of Gleevec. exon 17th and 13th mutations are put in place in terms of treatment response for the clinical significance while they are rarely seen.

The scientific studies of KIT and PDGFRA genes show mutations are concentrated in some specific points. Although frequently exon 11 mutations established (67% of all GISTs) in KIT gene these facts have a great response for treatment. Furthermore exon 9 has mutations with a second class frequency (%10). The cases which have mutations in this region have been put in the scientific datas that the high dose should be used (800mg/day) rather than usage of standart dose (800mg/day).

Research studies in the PDGFRA gene identified especially the 12th exon mutations were so important in terms of patients treatment response receiving. However 18th exon mutations differ for the purposes of clinical evidence. Some mutations in this region respond to imatinib therapy while some mutations are in the opposite case. In the presence of D842V mutation the resistance against imatinib observed at this phenomenon especially in 4-5% of all GIS tumors. Other drugs are recommended in this type of cases treatment protocol.

In our center, KIT and PDFGRA gene region determination studies that lead to GIST treatment prtocols have been started during 2006 and finalized in 2007. In accordance with scientific data, the investigation of 9th, 11th, 13th exons in KIT gene and 17th, 12th and 18th exons in PDGFRA gene have been set-up. Beginning from June 2007 our center can detect mutations at these regions with DNA sequence analysis method.