title: Strong expression of IGF1R in pediatric gastrointestinal stromal tumors without IGF1R genomic amplification.
abstract: Wildtype (WT) gastrointestinal stromal tumors (GISTs), lacking mutations in KIT or PDGFRA, represent 85% of GISTs in pediatric patients. Treatment options for pediatric WT GIST are limited. Recently, expression profiling of a limited number of pediatric and adult WT GISTs and more in depth study of a single pediatric WT GIST implicated the insulin-like growth factor 1 receptor (IGF1R) as a potential therapeutic target in pediatric WT GIST. We performed immunoblotting, SNP and FISH studies to determine the extent of expression, biochemical activation and genomic amplification of IGF1R in a larger number of pediatric WT GISTs. Pediatric WT GISTs expressed IGF1R strongly, whereas typical adult KIT mutant GISTs did not. IGF1R gene amplification was not detected in pediatric WT GISTs, and some KIT-mutant GISTs had IGF1R gene deletion due to monosomy 15. Despite the absence of apparent genomic activation mechanisms accounting for overexpression, clinical study of IGF1R-directed therapies in pediatric WT GIST is warranted.
authors.affiliation: Department of Pediatric Hematology-Oncology, Dana Farber Cancer Institute and Children's Hospital, Boston, MA 02115, USA. katherine_janeway@dfci.harvard.edu
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Janeway
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Jordi
authors.initials: J
authors.lastname: Barretina
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez-Atayde
authors.forename: George D
authors.initials: GD
authors.lastname: Demetri
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D002648:Child; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism*; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D017526:Receptor, IGF Type 1