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Series GSE21530 Query DataSets for GSE21530
Status Public on May 20, 2010
Title PAIS experiment
Organism Homo sapiens
Experiment type Genome variation profiling by genome tiling array
Summary Intimal sarcoma (IS) is a rare, malignant and aggressive tumor that shows a relentless course with a concomitant low survival rate, for which no effective treatment is available. In this study, 21 cases of large arterial blood vessel IS were analyzed by immunohistochemistry and fluorescent in situ hydridisation (FISH), and selectively by karyotyping, array-CGH, sequencing, phospho-kinase antibody arrays and Western immunoblotting, in search for the novel diagnostic markers and potential molecular targets. Ex vivo immunoassays were applied to test the sensitivity of IS primary tumor cells to the receptor tyrosine kinase (RTK) inhibitors imatinib and dasatinib.We demonstrated that amplification of the platelet-derived growth factor receptor alpha (PDGFRA) is a common finding in IS, and might be considered as a cytogenetic hallmark of this entity. This amplification is consistently associated with PDGFRA activation. Furthermore, the tumors reveal persistent activation of the epidermal growth factor receptor (EGFR), concurrent to PDGFRA activation. Activated PDGFRA and EGFR frequently co-exist with amplification and overexpression of MDM2. Ex vivo immunoassays on primary cells showed the potency of dasatinib to inhibit PDGFRA and downstream effectors in IS. Our findings provide a rationale for investigating therapies that target PDGFRA, EGFR or MDM2 in IS. Given the molecular heterogeneity of this tumor type and the potential crosstalk between PDGFRA and EGFR signaling pathways, targeting multiple RTKs and aberrant downstream effectors might be required to improve therapeutic outcome for patients with this disease.

Key words: intimal sarcoma, PDGFRA, EGFR, MDM2, targeted therapy, amplification
 
Overall design Genomic profiling of 8 PAIS cases for detection of chormosomal aberrations
Individual sample Against a normal control
 
Contributor(s) Finalet J
Citation(s) 20685895
Submission date Apr 27, 2010
Last update date Oct 26, 2016
Contact name Julio Finalet
E-mail(s) julio.finaletferreiro@med.kuleuven.be
Organization name KULeuven
Street address Herestraat 49
City Leuven
ZIP/Postal code 3000
Country Belgium
 
Platforms (1)
GPL4091 Agilent-014693 Human Genome CGH Microarray 244A (Feature number version)
Samples (8)
GSM537760 Pulmonary artery intimal sarcoma 1
GSM537761 Pulmonary artery intimal sarcoma 2
GSM537762 Pulmonary artery intimal sarcoma 3
Relations
BioProject PRJNA125933

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21530_RAW.tar 196.0 Mb (http)(custom) TAR (of TXT)
GSE21530_Suppl_Table_1_aCGH_results.pdf.gz 173.3 Kb (ftp)(http) PDF
Processed data included within Sample table

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