PURPOSE: Mutated KIT and platelet-derived growth factor alpha gene (PDGFRA) drive GI stromal tumor (GIST) oncogenesis, but the clinical significance of their single mutations is known incompletely. PATIENTS AND METHODS: We identified 11 population-based series of patients with GIST through a literature search and pooled individual data from 3,067 patients treated with macroscopically complete tumor excision. Mutation analysis was done from 1,505 tumors. We analyzed associations between KIT and PDGFRA mutations and recurrence-free survival (RFS) in the subsets in which patients were treated with surgery alone. RESULTS: We identified 301 different single mutations in KIT and 33 in PDGFRA. Patients with PDGFRA mutations had more favorable RFS than those with KIT mutations (hazard ratio, 0.34; P = .004). Only one of the 35 GISTs with KIT exon 11 duplication mutations recurred. Patients with deletions of only one codon of KIT exon 11 had better RFS than those with another deletion type, and some KIT exon 11 substitution mutations (Trp557Arg, Val559Ala, and Leu576Pro) were also associated with favorable RFS. Patients with an identical mutation had greatly variable outcomes depending on the standard prognostic factors, notably, mitotic count. Commonly used risk stratification schemes tended to overestimate the risk for recurrence in subgroups with prognostically favorable mutations. CONCLUSION: GISTs with an identical KIT or PDGFRA mutation may have widely varying risks for recurrence. Most of the patients with PDGFRA mutations and those with KIT exon 11 duplication mutation or deletion of one codon have favorable RFS with surgery alone and are usually not candidates for adjuvant therapy.
- MeSH
- dítě MeSH
- dospělí MeSH
- gastrointestinální nádory enzymologie genetika chirurgie MeSH
- gastrointestinální stromální tumory enzymologie genetika chirurgie MeSH
- genetická predispozice k nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru enzymologie genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- protoonkogenní proteiny c-kit genetika MeSH
- růstový faktor odvozený z trombocytů - receptor alfa genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- antiemetika * terapeutické užití MeSH
- časové faktory MeSH
- cílená molekulární terapie MeSH
- gastrointestinální nádory * enzymologie farmakoterapie genetika mortalita patologie MeSH
- imunoterapie * metody škodlivé účinky MeSH
- kongresy jako téma MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery * genetika MeSH
- nauzea * chemicky indukované prevence a kontrola MeSH
- přežití po terapii bez příznaků nemoci MeSH
- progrese nemoci MeSH
- protokoly antitumorózní kombinované chemoterapie * škodlivé účinky terapeutické užití MeSH
- protoonkogenní proteiny B-raf * genetika MeSH
- výsledek terapie MeSH
- zvracení * chemicky indukované prevence a kontrola MeSH
- Check Tag
- lidé MeSH
