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E-GEOD-36001 - Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma [gene expression]

Released on 6 December 2012, last updated on 2 June 2014
Homo sapiens
Samples (25)
Array (1)
Protocols (7)
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. Comparison of gene expression patterns in 19 osteosarcoma cell lines and 6 normal samples (osteoblasts and bones)
Experiment type
transcription profiling by array 
Leonardo A. Meza-Zepeda <>, Ana H Barragan-Polania, Anne-Marie Cleton-Jansen, Eivind Hovig, Halfdan Rydbeck, Heidi M Namløs, Knut Liestøl, Leonardo A Meza-Zepeda, Magne Skårn, Ola Myklebost, Stine H Kresse
Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma. Kresse SH, Rydbeck H, Sk�rn M, Naml�s HM, Barragan-Polania AH, Cleton-Jansen AM, Serra M, Liest�l K, Hogendoorn PC, Hovig E, Myklebost O, Meza-Zepeda LA. , PMID:23144859
Investigation descriptionE-GEOD-36001.idf.txt
Sample and data relationshipE-GEOD-36001.sdrf.txt
Processed data (1)
Additional data (1)
Array designA-MEXP-930.adf.txt