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Series GSE88826 Query DataSets for GSE88826
Status Public on Jan 30, 2017
Title DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.
 
Overall design DNA methylation sequencing for a cohort of 140 Ewing sarcoma tumor samples, 16 Ewing sarcoma cell lines, and 32 primary mesenchymal stem cell samples
 
Contributor(s) Bock C
Citation(s) 28134926
Submission date Oct 17, 2016
Last update date May 15, 2019
Contact name Christoph Bock
E-mail cbock@cemm.oeaw.ac.at
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (188)
GSM2471502 EWS_T1
GSM2471503 EWS_T2
GSM2471504 EWS_T3
Relations
BioProject PRJNA349025
SRA SRP091715

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
GSE88826_RAW.tar 5.9 Gb (http)(custom) TAR (of TXT)
Raw data are available in SRA
Processed data provided as supplementary file

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