IGF2 over-expression in solitary fibrous tumours is independent of anatomical location and is related to loss of imprinting.
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.
Hajdu
Mihai
M
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Singer
Samuel
S
Maki
Robert G
RG
Schwartz
Gary K
GK
Keohan
Mary Lou
ML
Antonescu
Cristina R
CR
D000328:Adult; D000368:Aged; D016000:Cluster Analysis; D000070819:Discoidin Domain Receptor 1; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D054364:Solitary Fibrous Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D000070819:Discoidin Domain Receptor 1; D007335:Insulin-Like Growth Factor II; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C117597:CEP43 protein, human; C035170:IGF2 protein, human; C092030:DDR1 protein, human; C508053:ERBB2 protein, human