IGF2 over-expression in solitary fibrous tumours is independent of anatomical location and is related to loss of imprinting

Hajdu, M., Singer, S., Maki, R. G., Schwartz, G. K., Keohan, M. L., Antonescu, C. R. (July 2010) IGF2 over-expression in solitary fibrous tumours is independent of anatomical location and is related to loss of imprinting. J Pathol, 221 (3). pp. 300-7. ISSN 1096-9896 (Electronic)0022-3417 (Linking)

Abstract

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm composed of CD34-positive fibroblastic cells. The pathogenesis driving this neoplasm remains unclear, with no recurrent genetic aberrations described to date. Previous reports suggest a role for IGF2 over-expression in the pathogenesis of these tumours, implicated in triggering hypoglycaemia in some patients. The expression profiling of 23 SFTs was investigated using an Affymetrix U133A platform. The transcriptional signature was compared to a set of 34 soft tissue sarcomas spanning seven subtypes. Potential candidate genes were then further investigated for activating mutations or loss of imprinting (LOI). SFT had a distinct expression signature and clustered in a tight genomic cluster, separate from all other sarcoma subtypes. A number of over-expressed receptor tyrosine kinase (RTK) genes were identified in SFT, including DDR1, ERBB2 and FGFR1; however, no mutations were identified by cDNA sequencing. Over-expression of IGF2 was uniformly detected in SFT, regardless of anatomical location, and was related to LOI. In contrast, IGF1 and JUN over-expression was seen in pleural, but not meningeal, locations. SFT shows a distinctive expression signature, with over-expression of DDR1, ERBB2 and FGFR1. Despite of lack of activating mutations in these RTKs, therapy with specific inhibitors targeting these kinases might be considered in advanced/metastatic cases. Our results confirm LOI in several tumours expressing high levels of IGF2, which may explain the observed paraneoplastic hypoglycaemia.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Cluster Analysis Female Gene Expression Profiling/methods Genomic Imprinting Humans Insulin-Like Growth Factor II/genetics/*metabolism Male Middle Aged Mutation Neoplasm Proteins/metabolism Proto-Oncogene Proteins/metabolism Receptor Protein-Tyrosine Kinases/metabolism Receptor, ErbB-2/metabolism Signal Transduction/genetics Solitary Fibrous Tumors/genetics/*metabolism/pathology
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > ErbB
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > IGF
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: July 2010
Date Deposited: 21 Oct 2016 19:58
Last Modified: 21 Oct 2016 19:58
PMCID: PMC3264680
Related URLs:
URI: https://repository.cshl.edu/id/eprint/33709

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