KIT and PDGFRA Mutations and the Risk of GI Stromal Tumor Recurrence

Autoři	JOENSUU Heikki RUTKOWSKI Piotr NISHIDA Toshirou STEIGEN Sonja E. BRABEC Petr PLANK Lukas NILSSON Bengt BRACONI Chiara BORDONI Andrea MAGNUSSON Magnus K. SUFLIARSKY Jozef FEDERICO Massimo JONASSON Jon G. HOSTEIN Isabelle BRINGUIER Pierre Paul EMILE Jean Francois
Rok publikování	2015
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of clinical oncology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1200/JCO.2014.57.4970
Obor	Onkologie a hematologie
Klíčová slova	KIT and PDGFRA mutations; risk of GI stromal tumor recurrence
Popis	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.