Comment[ArrayExpressAccession] E-GEOD-45240 MAGE-TAB Version 1.1 Public Release Date 2013-10-10 Investigation Title Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer [Methylation profiling by array] Comment[Submitted Name] Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer [Methylation profiling by array] Experiment Description Genetic and epigenetic alterations are essential for the initiation and progression of human cancer. We previously reported that primary human medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation in critical developmental pathways. To determine whether genetically engineered mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In contrast to human samples, very few loci with cancer-specific DNA hypermethylation were detected, and in almost all cases the degree of methylation was relatively modest compared to the dense hypermethylation in the human cancers. To determine if this finding was common to other GEMMs, we examined a Burkitt lymphoma and breast cancer model and did not detect promoter CpG island DNA hypermethylation, suggesting that human cancers and at least some GEMMs are fundamentally different with respect to this epigenetic modification. These findings provide an opportunity to both better understand the mechanism of aberrant DNA methylation in human cancer and construct better GEMMs to serve as preclinical platforms for therapy development. Genome-wide DNA methylation profiles generated using the Denaturation Analysis of Methylation Differences (DAMD) assay of cancer versus normal samples. 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 Diede Diede Yao Keyes Tyler Dey Hackett Elsaesser Kemp Neiman Weiss Olson Tapscott Person First Name Scott Scott Zizhen C Ashlee Joyoti Christopher Katrina Christopher Paul William James Stephen Person Mid Initials J. J C E S J E A M J Person Email sjdiede@fhcrc.org Person Affiliation Fred Hutchinson Cancer Research Center Person Address Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mailstop c3-168, Seattle, WA, USA Person Roles submitter Protocol Name P-GSE45240-2 P-GSE45240-3 P-GSE45240-1 P-GSE45240-4 Protocol Description Samples (7.5μg of DNA) were enzymatically fragmented and labeled using the WT Labeling Kit (Affymetrix) to add biotinylated compound to the ends of the fragments. Approximately 7.5μg of DNA was hybridzed per array using the Affymetrix hybridization kit. Arrays were hybridized for 16 hours at 45° at 60rpm using an Affymetrix hybridization oven. Genomic DNA was extracted from cell lines, primary human medulloblastoma, normal cerebellum, and mouse tumors using a QIAGEN Blood & Cell Culture DNA kit per manufacturer's instructions. The DAMD assay was performed as described (Mahoney SE, Yao Z, Keyes CC, Tapscott SJ, & Diede SJ (2012). Genome-wide DNA methylation studies suggest distinct DNA methylation patterns in pediatric embryonal and alveolar rhabdomyosarcomas. Epigenetics 7(4)). Arrays were scanned on an Affymetrix Scanner 3000 7G Protocol Type labelling protocol hybridization protocol nucleic acid extraction protocol array scanning protocol Experimental Factor Name CELL LINE CELL TYPE ORGANISM PART ORGANISM Experimental Factor Type cell line cell type organism part organism Publication Title Fundamental differences in promoter CpG island DNA hypermethylation between human cancer and genetically engineered mouse models of cancer. Publication Author List Diede SJ, Yao Z, Keyes CC, Tyler AE, Dey J, Hackett CS, Elsaesser K, Kemp CJ, Neiman PE, Weiss WA, Olson JM, Tapscott SJ PubMed ID 24107773 Comment[SecondaryAccession] GSE45240 Comment[GEOReleaseDate] 2013-10-10 Comment[ArrayExpressSubmissionDate] 2013-03-18 Comment[GEOLastUpdateDate] 2013-10-11 Comment[AEExperimentType] methylation profiling by array Comment[AdditionalFile:Data1] GSE45240_hWBC_rep1.CEL Comment[AdditionalFile:Data2] GSE45240_hWBC_rep2.CEL Comment[AdditionalFile:Data3] GSE45240_mBrCON_rep1.CEL Comment[AdditionalFile:Data4] GSE45240_mBrCON_rep2.CEL Comment[AdditionalFile:Data5] GSE45240_mMFp4_F_rep1.CEL Comment[AdditionalFile:Data6] GSE45240_mMFp4_F_rep2.CEL Comment[AdditionalFile:Data7] GSE45240_mMFp4_rep1.CEL Comment[AdditionalFile:Data8] GSE45240_mMFp4_rep2.CEL Comment[AdditionalFile:Data9] GSE45240_mTumor1_rep1.CEL Comment[AdditionalFile:Data10] GSE45240_mTumor1_rep2.CEL Comment[AdditionalFile:Data11] GSE45240_mTumor3_rep1.CEL Comment[AdditionalFile:Data12] GSE45240_mTumor3_rep2.CEL Comment[AdditionalFile:Data13] GSE45240_mTumor4_rep1.CEL Comment[AdditionalFile:Data14] GSE45240_mTumor4_rep2.CEL Comment[AdditionalFile:Data15] GSE45240_mWTCblSmoA1_rep1.CEL Comment[AdditionalFile:Data16] GSE45240_mWTCblSmoA1_rep2.CEL Comment[AdditionalFile:Data17] GSE45240_mWTCblSmoA2_rep1.CEL Comment[AdditionalFile:Data18] GSE45240_mWTCblSmoA2_rep2.CEL Comment[AdditionalFile:Data19] GSE45240_mWTmsn_rep1.CEL Comment[AdditionalFile:Data20] GSE45240_mWTmsn_rep2.CEL Comment[AdditionalFile:Data21] GSE45240_mWTspleen_rep1.CEL Comment[AdditionalFile:Data22] GSE45240_mWTspleen_rep2.CEL SDRF File E-GEOD-45240.sdrf.txt