Comment[ArrayExpressAccession]	E-GEOD-38235
MAGE-TAB Version	1.1											
Public Release Date	2013-06-04
Investigation Title	Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia											
Comment[Submitted Name]	Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia
Experiment Description	B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic origin of the disease remains unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. We assessed the DNA methylation status of 402,842 CpG-sites across the genome (Illumina 450k array) in tumor and remission samples of 46 pre-B ALL patients, thus generating the most comprehensive single CpG-site resolution pre-B ALL methylomes so far. Unsupervised hierarchical clustering of CpG-site neighborhood, protein-coding gene, or miRNA gene associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CpG islands, shores, and in regions around the transcription start site of protein-coding genes strongly correlated with transcript expression. Focusing on samples carrying the t(12;21)(p13;q22) translocation (ETV6-RUNX1 fusion gene) we identified subtype-specific methylation of 430 CpG-sites. Pathway analyses implied the associated genes in hematopoiesis and cancer. Further intersection with transcriptome data identified methylation to impact expression of 18 genes. In summary, our data illustrate the power of methylation profiling to classify leukemic subtypes and to identify subtype-specific methylation markers. Further, we demonstrate that integration of methylome and transcriptome alterations allows the study of downstream effects of individual genomic rearrangements in cancer. Bisulfite converted DNA of tumor (isolated on day of diagnosis) and remission (isolated after disease remission) samples derived from 46 patients of French-Canadian origin diagnosed with pre-B ALL were analyzed on the Illumina Infinium HumanMethylation 450k BeadChips.											
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl										
Person Last Name	Busche	Busche	Ge	Vidal	Spinella	Saillour	Richer	Healy	Chen	Droit	Sinnett	Pastinen
Person First Name	Stephan	Stephan	Bing	Ramon	Jean-François	Virginie	Chantal	Jasmine	Shu-Huang	Arnaud	Daniel	Tomi
Person Email	geo@ncbi.nlm.nih.gov											
Person Affiliation	McGill University											
Person Address	Human Genetics, McGill University, 740 Dr. Penfield Avenue, Montreal, Quebec, Canada											
Person Roles	submitter											
Protocol Name	P-GSE38235-1	P-GSE38235-5	P-GSE38235-6	P-GSE38235-2	P-GSE38235-3	P-GSE38235-4	P-GSE38235-7					
Protocol Description	GenomeStudio Software V2011.1 ID_REF =  VALUE = Average Beta Detection_Pval = 	standard Illumina protocol	bisulphite converted DNA was amplified, fragmented and hybridised to Illumina Infinium Human Methylation450k Beadchip using standard Illumina protocol	tumor samples: NA; remission samples: patients underwent treatment with uniform Dana-Farber Cancer Institute ALL Consortium protocols DFCI 95-01, 2000-01 or 2005-01.	primary cells isolated from patient's blood or bone marrow	genomic DNA was isolated from frozen cell pellets using the genomic DNA purification kit (Gentra Systems), and 500 ng gDNA were used as input for bisulfite conversion employing the EZ DNA Methylation Kit (Zymo Research), all according to manufacturer’s protocol.	arrays were imaged using iScan Reader using standard recommended Illumina scanner setting					
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	growth protocol	nucleic acid extraction protocol	array scanning protocol					
Experimental Factor Name	TUMOR SUBTYPE	DISEASE STATE	SEX									
Experimental Factor Type	tumor subtype	disease state	sex									
Publication Title	Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia.											
Publication Author List	Busche S, Ge B, Vidal R, Spinella JF, Saillour V, Richer C, Healy J, Chen SH, Droit A, Sinnett D, Pastinen T											
PubMed ID	23722552											
Publication DOI	10.1158/0008-5472.CAN-12-4367											
Comment[SecondaryAccession]	GSE38235											
Comment[GEOReleaseDate]	2013-06-04											
Comment[ArrayExpressSubmissionDate]	2012-05-24											
Comment[GEOLastUpdateDate]	2013-06-06											
Comment[AEExperimentType]	methylation profiling by array											
Comment[AdditionalFile:Data1]	GSE38235_non-normalized.txt											
SDRF File	E-GEOD-38235.sdrf.txt