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Medline ® Abstract for Reference 93

of 'Epidemiology, classification, clinical presentation, prognostic features, and diagnostic work-up of gastrointestinal mesenchymal neoplasms including GIST'

KIT and PDGFRA mutations and the risk of GI stromal tumor recurrence.
Joensuu H, Rutkowski P, Nishida T, Steigen SE, Brabec P, Plank L, Nilsson B, Braconi C, Bordoni A, Magnusson MK, Sufliarsky J, Federico M, Jonasson JG, Hostein I, Bringuier PP, Emile JF
J Clin Oncol. 2015 Feb;33(6):634-42. Epub 2015 Jan 20.
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 andthose 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.
Heikki Joensuu, Helsinki University Central Hospital, Helsinki, Finland; Piotr Rutkowski, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Toshirou Nishida, National Cancer Center Hospital East, Kashiwa, Japan; Sonja E. Steigen, University Hospital of North Norway and Tumor Biology Research Group, UiT The Arctic University of Norway, Tromsø, Norway; Peter Brabec, Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic; Lukas Plank, Jessenius Medical Faculty of Comenius University and University Hospital, Martin; Jozef Sufliarsky, National Cancer Institute, Bratislava, Slovak Republic; Bengt Nilsson, Sahlgrenska University Hospital, Gothenburg, Sweden; Chiara Braconi, Centro Regionale di Genetica Oncologica, Oncologia Medica, Ancona; Massimo Federico, University of Modena and Reggio Emilia, Modena, Italy; Chiara Braconi, The Institute of Cancer Research, Belmont, United Kingdom; Andrea Bordoni, Ticino Cancer Registry, Insitute of Pathology South of Switzerland, Locarno, Switzerland; Magnus K. Magnusson, University of Iceland; Jon G. Jonasson, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland; Isabelle Hostein, BergoniéInstitute, Bordeaux; Pierre-Paul Bringier, E. Herriot Hospital, Lyon; Jean-Francois Emile, Versailles University and Assistance Publique-Hôpitaux de Paris, Ambroise ParéHospital, Boulogne, France. heikki.joensuu@hus.fi.