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Series GSE59678 Query DataSets for GSE59678
Status Public on Jul 24, 2014
Title Affymetrix SNP 250K array data for paediatric high grade gliomas
Organism Homo sapiens
Experiment type SNP genotyping by SNP array
Summary Alkylating agents are a frontline therapy for the treatment of several cancers including pediatric glioblastoma, a devastating lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed; increasing therapeutic response while minimizing toxicity. Here we report using a siRNA screen targeting over 240 DNA damage response genes identified novel sensitizers to alkylating agents. In particular the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM) were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors.
 
Overall design Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from snap frozen biopsy and surgical brain tissue from paediatric high grade gliomas
Copy number analysis on Affymetrix SNP 250K arrays was performed for 35 paediatric high grade glioma samples and HapMap samples.
 
Contributor(s) Agnihotri S, Burrell K, Buczkowicz P, Remke M, Golbourn B, Chornenkyy Y, Gajadhar A, Fernandez NA, Clarke ID, Barszczyk MS, Pajovic S, Ternamian C, Head R, Sabha N, Sobol RW, Taylor MD, Rutka JT, Jones C, Dirks PB, Zadeh G, Hawkins C
Citation(s) 25100205
Submission date Jul 22, 2014
Last update date May 17, 2017
Contact name Pawel Buczkowicz
E-mail(s) pawel.buczkowicz@sickkids.ca
Organization name Hospital for Sick Children
Department Paediatric Laboratory Medicine
Lab BTRC
Street address 686 Bay Street
City Toronto
State/province Ontario
ZIP/Postal code M5G 0A4
Country Canada
 
Platforms (1)
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
Samples (35)
GSM1442611 High Grade Astrocytoma 1 - Tumour-250Knsp
GSM1442612 High Grade Astrocytoma 2 - Tumour-250Knsp
GSM1442613 High Grade Astrocytoma 3 - Tumour-250Knsp
Relations
BioProject PRJNA255983

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
GSE59678_RAW.tar 1.0 Gb (http)(custom) TAR (of CEL, CHP)
GSE59678_processed_data_for_each_SNP_allele.txt.gz 66.2 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record
Processed data provided as supplementary file

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