Patterns of deregulation of insulin growth factor signalling pathway in paediatric and adult gastrointestinal stromal tumours Journal Article
| Authors: | Italiano, A.; Chen, J.; Zhang, L.; Hajdu, M.; Singer, S.; DeMatteo, R. P.; Antonescu, C. R. |
| Article 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. Conclusion: 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. © 2012 Elsevier Ltd. All rights reserved. |
| Keywords: | signal transduction; adult; child; human tissue; protein expression; young adult; gene mutation; major clinical study; mutation; genetic analysis; gastrointestinal stromal tumor; imatinib; gastrointestinal stromal tumors; gene expression; gene expression profiling; age factors; platelet derived growth factor receptor; dna methylation; cancer resistance; receptor, igf type 1; gastrointestinal neoplasms; gene expression regulation, neoplastic; soft tissue sarcoma; gist; age of onset; somatomedin b; igf2; insulin-like growth factor ii; gastrointestinal stromal tumour; igf1r |
| Journal Title: | European Journal of Cancer |
| Volume: | 48 |
| Issue: | 17 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2012-11-01 |
| Start Page: | 3215 |
| End Page: | 3222 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2012.05.021 |
| PROVIDER: | scopus |
| PUBMED: | 22770876 |
| PMCID: | PMC3564499 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: EJCAE" - "Source: Scopus" |
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