Comment[ArrayExpressAccession] E-GEOD-41842 MAGE-TAB Version 1.1 Public Release Date 2012-10-27 Investigation Title Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway Comment[Submitted Name] Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway Experiment Description Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes. miRNA profiling of medulloblastomas was carried out using Taqman Low Density Density Aarray v 1.0 having 365 human microRNAs. In parallel, genome--wide expression profiling of protein coding genes was carried out using Affymetrix gene 1.0 ST arrays. Both the profiling studies identified four molecular subtypes of medulloblastomas. Expression levels of select protein-coding genes and miRNAs could classify an independent set of medulloblastomas. Twelve of 31 medulloblastomas were found to overexpress genes belonging to the canonical WNT signaling pathway and carry a mutation in CTNNB1 gene. A number of miRNAs like miR-193a, miR-224/miR-452 cluster, miR-182/miR-183/miR-96 cluster, and miR-148a having potential tumor/metastasis suppressive activity were found to be overexpressed in the WNT signaling associated medulloblastomas. Exogenous expression of miR-193a and miR-224, two miRNAs that have the highest WNT pathway specific upregulation, was found to inhibit proliferation, increase radiation sensitivity and reduce anchorage-independent growth of medulloblastoma cells. Expression level of tumor/metastasis suppressive miRNAs in the WNT signaling associated medulloblastomas is likely to determine their response to treatment, and thus, these miRNAs would be important biomarkers for risk stratification within the WNT signaling associated medulloblastomas. A total of 19 human sporadic medulloblastomas were profiled using the Affymetrix Gene 1.0 ST array 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 Shirsat Gokhale Kunder Goel Sarin Moiyadi Shenoy Mamidipally Noronha Kannan Shirsat Person First Name Neelam A R A R A A C S S N Person Mid Initials V V Person Email nshirsat@actrec.gov.in Person Affiliation Advanced Centre for Treatment, Research and Education in Cancer. Tata Memorial Centre Person Address Shirsat Lab, Advanced Centre for Treatment, Research and Education in Cancer. Tata Memorial Centre, Kharghar, Sector 21, Navi Mumbai, Maharashtra, India Person Roles submitter Protocol Name P-GSE41842-1 P-GSE41842-5 P-GSE41842-4 P-GSE41842-2 P-GSE41842-3 P-GSE41842-6 Protocol Description ID_REF = VALUE = log2 GCRMA normalised value GeneChips were scanned using the Affymetrix GeneChip scanner 2500. Following fragmentation, 2 ug cRNA was hybridized for 16 hr at 45M-0C on Gene 1.0 ST Array. GeneChips were washed and stained in the Affymetrix Fluidics Station Total RNA was extracted from tumor tissues using the mirVANA kit ( Ambion, Austin, TX, USA) , as per the manufacturerM-bM-^@M-^Ys protocol after ensuring at least 80% tumor cell content.The RNA was further purified using RNeasy columns (Qiagen,Valencia, CA, USA), for removing genomic DNA contamination if at all . RNAs having more than 7.0 RIN value and no detectable genomic DNA contamination were used for the analysis. 100 ng total RNA was reverse transcribed, amplified, and labeled with biotin using the whole transcript sense target labeling kit as per the manufacturerM-bM-^@M-^Ys instructions (Affymetrix, Santa Clara, CA, USA). Data normalization was done using GCRMA algorithm in the Bioconductor package (v 2.1) of the R statistical environment (http://www.bioconductor.org) Protocol Type bioassay_data_transformation image_aquisition hybridization nucleic_acid_extraction labeling feature_extraction Experimental Factor Name MOLECULAR SUBGROUP AGE YR SEX Experimental Factor Type molecular subgroup age yr sex Publication Title Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway. Publication Author List Gokhale A, Kunder R, Goel A, Sarin R, Moiyadi A, Shenoy A, Mamidipally C, Noronha S, Kannan S, Shirsat NV PubMed ID 21358093 Publication DOI 10.4103/0973-1482.77072 Comment[SecondaryAccession] GSE41842 Comment[GEOReleaseDate] 2012-10-27 Comment[ArrayExpressSubmissionDate] 2012-10-26 Comment[GEOLastUpdateDate] 2012-11-02 Comment[AEExperimentType] transcription profiling by array SDRF File E-GEOD-41842.sdrf.txt