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Series GSE36003 Query DataSets for GSE36003
Status Public on Dec 06, 2012
Title Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma [DNA copy number]
Organism Homo sapiens
Experiment type Genome variation profiling by SNP array
Summary Osteosarcomas are the most common primary malignant tumours of bone, and almost all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. The cell lines showed complex patterns of DNA copy number changes, where copy number gains were significantly associated with gene-rich regions of the genome and losses with gene-poor areas. Integration of the datasets showed that the mRNA levels were regulated by either alterations in DNA copy number or DNA methylation. Using a recurrence threshold of 6/19 (> 30 %) cell lines, 348 genes were identified as having alterations of two data types (gain or hypo-methylation/over-expression, loss or hyper-methylation/under-expression). These genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2’-deoxycytidine treatment for all four genes tested. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for some genes. Integrative analysis of genome-wide genetic and epigenetic alterations identified mechanistic dependencies and relationships between DNA copy number and DNA methylation in terms of regulating mRNA expression levels in osteosarcomas, contributing to better understanding of osteosarcoma biology.
Overall design Comparison of DNA copy number changes in 19 osteosarcoma cell lines
Contributor(s) Kresse SH, Rydbeck H, Skårn M, Namløs HM, Barragan-Polania AH, Cleton-Jansen A, Liestøl K, Hovig E, Myklebost O, Meza-Zepeda LA
Citation(s) 23144859
Submission date Feb 22, 2012
Last update date Nov 27, 2018
Contact name Leonardo A. Meza-Zepeda
Organization name The Norwegian Radium Hospital
Department Dept. of Tumor Biology
Street address Ullernchausseen 70
City Oslo
ZIP/Postal code N-0310
Country Norway
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (19)
GSM879206 Osteosarcoma cell line 143B [copy number]
GSM879207 Osteosarcoma cell line HAL [copy number]
GSM879208 Osteosarcoma cell line HOS [copy number]
This SubSeries is part of SuperSeries:
GSE36004 Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma.
BioProject PRJNA155745

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Supplementary file Size Download File type/resource
GSE36003_RAW.tar 780.8 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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