KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs)

摘要: Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, their understanding is becoming increasingly important, because specific treatment targeting oncogenic activation (especially imatinib mesylate) has become available. clustered four exons. Most common exon 11 (juxtamembrane domain) that include deletions, point (affecting a few codons), duplications (mostly the 3' region). The latter most often occur gastric GISTs. Among GISTs, tumors with deletions more aggressive than those mutations; this does not seem to hold true small intestinal Exon 9 (5-10%) usually 2-codon 502-503 duplications, these predominantly versus Lesser sensitivity of been noted. Kinase domain very rare; GISTs such variably sensitive imatinib. especially epithelioid variants; overall frequency approximately 30% 40% mutation negative 18 leading Asp842Val at protein level. This causes resistance. 12 14 rare. somatic (in tumor tissue only), but patients familial syndrome have consitutitonal KIT/PDGFRA >10 families reported worldwide generally similar sporadic neurofibromatosis 1 patients, children, Carney triad lack GIST-specific may different disease mechanism. Secondary kinase domains after resulting resistance drug. Mutation genotyping tool diagnosis assessment inhibitors. US government work. There no restrictions on its use.