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| Status |
Public on Jun 01, 2010 |
| Title |
Human Exon Array Profiling of Ewing sarcoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Ewing sarcoma family tumors (ESFTs) are aggressive tumors of putative stem cell origin for which prognostic biomarkers and novel treatments are needed. We have previously shown that the polycomb gene BMI-1 functions as an oncogene in ESFT. In several human cancers, high expression of BMI-1 is associated with poor outcome. For the current study, we evaluated the significance of variable BMI-1 expression levels in a large cohort of primary ESFT. Immunohistochemical staining of 130 tumors revealed that BMI-1 is over-expressed by the vast majority of ESFT. However, in 20% of cases, BMI-1 levels are low to undetectable. Significantly, although clinical presentation and outcome were found to be similar between BMI-1-high and BMI-1-low tumors, gene expression profiling studies showed marked differences in their respective gene expression profiles. Gene specific enrichment analysis identified that several cancer-associated canonical biologic pathways, including IGF1, mTOR and WNT, are significantly down-regulated in BMI-1-low compared to BMI-1-high tumors. Consistent with these in vivo data, in vitro studies of IGF1-R inhibition showed that the growth inhibitory effects of IGF1-R blockade are diminished in BMI-1-low ESFT cells. ESFT that do not over-express BMI-1 represent a novel subclass with a distinct molecular profile and altered activation of cancer-associated pathways.
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| |
|
| Overall design |
Affy HuEx 1.0 array profiling of 10 primary ESFT samples obtained from patients with newly diagnosed ESFT. 5 confirmed BMI-1 low and 5 confirmed BMI-1 high expressers by immunostaining.
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| |
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| Contributor(s) |
Lawlor ER |
| Citation(s) |
21047978 |
| Submission date |
May 07, 2009 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Elizabeth R Lawlor |
| E-mail(s) |
elawlor@umich.edu
|
| Organization name |
University of Michigan
|
| Street address |
1600 Huron Parkway, NCRC Bldg 520
|
| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109-2800 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
|
| Samples (10)
|
|
| Relations |
| BioProject |
PRJNA115443 |
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