Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Methylation data from presentation and relapsed medulloblastoma tumour samples

ABSTRACT: We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse. We investigated the DNA methylation profiles of 18 diagnostic and 22 relapsing samples (including 15 diagnostic / relapse pairs) using the Illumina 450k methylation microarray

ORGANISM(S): Homo sapiens

SUBMITTER: Ed Schwalbe

PROVIDER: E-GEOD-62618 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

Hill Rebecca M RM Kuijper Sanne S Lindsey Janet C JC Petrie Kevin K Schwalbe Ed C EC Barker Karen K Boult Jessica K R JK Williamson Daniel D Ahmad Zai Z Hallsworth Albert A Ryan Sarra L SL Poon Evon E Robinson Simon P SP Ruddle Ruth R Raynaud Florence I FI Howell Louise L Kwok Colin C Joshi Abhijit A Nicholson Sarah Leigh SL Crosier Stephen S Ellison David W DW Wharton Stephen B SB Robson Keith K Michalski Antony A Hargrave Darren D Jacques Thomas S TS Pizer Barry B Bailey Simon S Swartling Fredrik J FJ Weiss William A WA Chesler Louis L Clifford Steven C SC

Cancer cell 20141218 1

We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this ...[more]

PMID: 25533335

Similar Datasets

Project description:Previously we have shown that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were restricted by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450K array). The array identified 444 differentially methylated CpG loci in dNK-treated EVT compared to medium control (P<0.05). The represented genes from these loci had critical biological roles in cellular development, cellular organization and maintenance by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltranferase IV) were chosen for follow-up studies because of the biological relevance found in the research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced, and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by siRNA reduced trophoblast invasion, possibly through the altered MMP-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduce protein expressions. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility. This studied analyzed 17 samples of placental villous explant cultre exposed to different growth conditions. 6 Control samples (biological replicates) were cultured and unexposed to any other cells. 5 samples (biological replicates and from the same placentas as the controls) were cultured and exposed to conditions containing decidua natural killer cells trapped inside hollow fibres (thus only the factors secreted by the cells could interact with the explant culture and not the cells themselves. 6 samples (biological replicates and from the same placentas as the controls) were cultured and exposed to media containing IL-15. The DNA from the villous explants was isolated, bisulfite converted and run on the array.

Dataset Information

Methylation data from presentation and relapsed medulloblastoma tumour samples

Publications

Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets