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| Status |
Public on Feb 16, 2011 |
| Title |
Gain of the oncostatin M receptor in cervical squamous cell carcinoma is associated with adverse clinical outcome [penn1Mb data] |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
For many oncogenes, increased expression resulting from copy number gain confers a selective advantage to cells that consequently make up the tumour bulk. To identify oncogenes of potential biological significance in cervical squamous cell carcinoma (SCC), 36 primary samples and ten cell lines were screened by array comparative genomic hybridization (CGH). The most commonly occurring regions of copy number gain that also showed amplification were 5p15.2–14.3 (59%), 5p13.3 (65%), and 5p13.2–13.1 (63%). Gene copy numbers were significantly associated with expression levels for three candidate oncogenes at these loci: OSMR (oncostatin M receptor) (p = 0.03), PDZK3 (PDZ domain containing protein 3) (p = 0.04), and TRIO (triple functional domain) (p = 0.03). Further examination by fluorescence in situ hybridization on a tissue microarray of 110 primary cervical SCC samples revealed copy number gain frequencies of 60.9%, 57.3%, and 54.5% for OSMR, PDZK3, and TRIO, respectively, with OSMR adversely influencing overall patient survival independently of tumour stage (p = 0.046). By array CGH, copy number gain of OSMR was not seen in any of 40 microdissected precursor cervical squamous intraepithelial lesions (SILs). Moreover, global mRNA expression analysis, using Affymetrix U133A 2.0 Arrays, showed no overexpression of OSMR in SILs, suggesting that OSMR gain and overexpression are relatively late steps in cervical carcinogenesis. In the cervical SCC cell lines CaSki and SW756, exogenous OSM activated downstream-signalling elements of OSMR including STAT3, p44/42 MAPK, and S6 ribosomal protein, and induced transcription of the angiogenic factor VEGF, effects that were reduced by OSMR depletion using RNA interference. We conclude that copy number gain of OSMR is frequently found in cervical SCC and is associated with adverse clinical outcome. As well as being a potential prognostic marker, OSMR is a candidate cell surface therapeutic target
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| Overall design |
36 primary cervical SCC samples, and 10 cervical SCC cell lines were subject to 1 Mb aCGH using a dye swapped approach. Two samples were subject to repeat. (J Pathol. 2007 Jul;212(3):325-34.)
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| Contributor(s) |
Ng G, Winder D, Muralidhar B, Gooding EL, Roberts I, Pett MR, Mukherjee G, Huang J, Coleman N |
| Citation(s) |
17516585 |
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| Submission date |
Feb 15, 2011 |
| Last update date |
Mar 23, 2012 |
| Contact name |
Ian Roberts |
| E-mail(s) |
ian.roberts@cantab.net
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| Phone |
0044 1223 763 279
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| Organization name |
Hutchison MRC Research Centre
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| Department |
Cancer Cell Unit
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| Lab |
Coleman
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| Street address |
Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0XZ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL13176 |
University of Pennsylvania/Nathanson Lab_HomoSapiens_5212 unique BACS_coleman_collaboration |
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| Samples (46)
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| This SubSeries is part of SuperSeries: |
| GSE27333 |
Gain of the oncostatin M receptor in cervical squamous cell carcinoma is associated with adverse clinical outcome |
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| Relations |
| BioProject |
PRJNA142097 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27331_RAW.tar |
93.4 Mb |
(http)(custom) |
TAR (of GPR) |
| GSE27331_TargetsCellLines.txt.gz |
231 b |
(ftp)(http) |
TXT |
| GSE27331_TargetsSILS.txt.gz |
764 b |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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