title: Patterns of deregulation of insulin growth factor signalling pathway in paediatric and adult gastrointestinal stromal tumours.
abstract: BACKGROUND
  Data regarding the patterns and the mechanisms of deregulation of the insulin growth factor (IGF) pathway in adult and paediatric gastrointestinal stromal tumours (GISTs) are limited.
  
  
  METHODS
  We investigated the expression profiling of the genes encoding the main components of the IGF signalling pathway in 131 GISTs (106 adults, 21 paediatric and four young adults) and 25 other soft-tissue sarcomas (STS) using an Affymetrix U133A platform. IGF2 was investigated for loss of imprinting (LOI) whereas IGF1R was analysed for copy number aberration and mutation.
  
  
  RESULTS
  IGF2 was the most highly overexpressed gene of the IGF pathway in GIST. IGF2 expression was also significantly higher than in other STS. IGF2 expression was correlated to the age onset and mutational status of GIST. Indeed, IGF2 expression was significantly higher in the 'adult' group than in the 'paediatric' and 'young adult' groups. Among adult GIST, IGF2 expression was higher in tumours lacking Homo sapiens v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) or alpha-type platelet-derived growth factor receptor (PDGFRA) mutations in comparison with mutated cases. A trend for a higher expression of IGF2 in resistant GIST in comparison to responsive GIST was also found. Overexpression of IGF2 was not related to LOI. Conversely, the expression of the IGF1R gene was significantly higher in the paediatric group than in the adult group. No copy number gains or mutations of IGF1R were observed.
  
  
  CONCLUSIONS
  The IGF pathway is deregulated in GIST with distinct patterns according to age onset and mutational status. The IGF pathway may represent a therapeutic target in patients with primary or secondary resistance to imatinib.
authors: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. italiano@bergonie.org
authors: Antoine
authors: A
authors: Italiano
authors: Junwei
authors: J
authors: Chen
authors: Lei
authors: L
authors: Zhang
authors: Mihai
authors: M
authors: Hajdu
authors: Samuel
authors: S
authors: Singer
authors: Ronald P
authors: RP
authors: DeMatteo
authors: Cristina R
authors: CR
authors: Antonescu
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D002648:Child; D019175:DNA Methylation; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D009154:Mutation; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
chemical_list: D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1