Status And Clinical Impficafion Of C-KIT And PDGFRA Mutations Ingastrointestinal Stromal Tumor(gist)

Objective: To explore the status of activating mutations of c-kit and PDGFRA in GIST of Chinese patients.Method: The clinic and pathological data of a series of patients with gastrointestinal stromal tumors in 2008-2009 yrs were analyzed retrospectively.Exon 9,11,13,17 of c-kit and exon 12,18 of PDGFRA were analyzed by direct sequencing.Results: c-kit mutations were detected in 70% of patients as follows:56.5% in exon 11,8.7% in exon 9,4.3% in exon 13 and none in exon 17. The c-kit exon 11 mutations were mostly heterogeneous and clustered in the classic"hot spot"at the 5;end of the exon, being in-frame deletion at Codon557-558. The second"hot spots"were internal tandem duplications(ITD) at the 3;end of the exon.PDGFRA mutations were present in13% (3/23) of CD117-negative GIST, two cases of exon 18 mutation,another in exon 12. The type of mutation was the commonest point mutation of D842V of exon 18.Conclusion: The vast majority of GIST in this study harbored c-kit and PDGFRA mutation. Most CD117 expressing GIST show c-kit mutations that are preferentially located in the classic hot spot and the second hot spot at the 3;end of exon 11. PDGFRA genic mutations are more likely seen in kit-negative GISTs arising in the stomach and have a high degree of invasion risk.