%0 Journal Article
%T Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors
%A Mara Silva
%A Isabel Veiga
%A Franclim R Ribeiro
%A Joana Vieira
%A Carla Pinto
%A Manuela Pinheiro
%A B¨¢rbara Mesquita
%A Catarina Santos
%A Marta Soares
%A Jos¨¦ Dinis
%A L¨²cio Santos
%A Paula Lopes
%A Mariana Afonso
%A Carlos Lopes
%A Manuel R Teixeira
%J BMC Medicine
%D 2010
%I BioMed Central
%R 10.1186/1741-7015-8-26
%X In the present study, somatic mutations in KIT and PDGFRA were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data.We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in KIT and 11.25% in PDGFRA. Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances were detected in 25 out of 29 tumors (86%), namely losses at 14q (88% of abnormal cases), 22q (44%), 1p (44%), and 15q (36%), and gains at 1q (16%) and 12q (20%). In addition to clinico-pathological high-risk groups, patients with KIT mutations, genomic complexity, genomic gains and deletions at either 1p or 22q showed a significantly shorter disease-free survival. Furthermore, genomic complexity was the best predictor of disease progression in multivariate analysis.In addition to KIT/PDGFRA mutational status, our findings indicate that secondary chromosomal changes contribute significantly to tumor development and progression of GIST and that genomic complexity carries independent prognostic value that complements clinico-pathological and genotype information.Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the gastrointestinal tract [1]. A diagnosis of GIST involves a multidisciplinary approach that combines clinical, pathological, and genetic features. Mutually exclusive activating mutations in KIT or PDGFRA occur in 85 to 90% of the cases and are considered primary events in GIST pathogenesis [1-3]. These genes encode type III transmembrane receptor proteins which, upon connection to their respective ligands, activate downstream signaling pathways involved in cell proliferation and survival [4-6
%U http://www.biomedcentral.com/1741-7015/8/26