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Series GSE48461 Query DataSets for GSE48461
Status Public on Aug 26, 2013
Title MGMT-STP27 methylation status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas; A report from EORTC study 26951
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Purpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of PCV after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.

Experimental Design: We performed genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status.

Results: We first demonstrate that methylation profiling can be performed on archival tissues with a performance that is similar to snap frozen tissue samples. We then performed methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared to CIMP- and/or MGMT-STP27 unmethylated tumors (median overall survival (OS) 1.05 v. 6.46 years and 1.06 v. 3.8 years, both P<0.0001 for CIMP and MGMT-STP27 status respectively). Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex performance score and review diagnosis in the model.Multivariate analysis indicates that CIMP and MGMT-STP27 status are prognostic factors for survival independent of age, sex, performance score and review diagnosis. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years respectively P=0.0033; for MGMT-STP27 methylated samples it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P=0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response.

Conclusions: MGMT-STP27 may be used to guide treatment decisions in this tumor type.
Overall design Bisulphite converted DNA from the 59 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

The following sample characteristics are provided;
OS: overall survival; PFS: progression free survival; CIMP: CpG Island Methylator phenotype; IGS: Intrinsic Glioma subtype; MGMT: O6-methylguanine-DNA-methyltransferase; OR diagn: original diagnosis; Rev diag: review diagnosis; Tum loc: Tumor location; Perf: Performance score; TRT: treatment
Performance is based on the ECOG performance status
Tum loc: tumor location indicated by 1: Biopsy; 2: Partial Resection; 3: Total Resection.
The MGMT promoter methylation status was determined previously (van den Bent et al, J. Clin Oncol 27: 5881-6, 2009) using MS-MLPA and may differ from the MGMT-SPT27 status.

***Please note that the non-normalized data provided for the records is incomplete, missing data for many probes***
Contributor(s) van den Bent MJ, Erdem-Eraslan L, Idbaih A, de Rooi J, Eilers PH, Spliet WG, den Dunnen WF, Tijssen C, Wesseling P, Sillevis Smitt PA, Kros JM, Gorlia T, French PJ
Citation(s) 23948976
Submission date Jul 01, 2013
Last update date Mar 22, 2019
Contact name Pim French
Phone +31 10 70443 33
Organization name Erasmus MC
Department Neurology
Lab Neurooncology
Street address Dr Molewaterplein 50
City Rotterdam
ZIP/Postal code 2040CA
Country Netherlands
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (59)
GSM1179282 Xpatid_48
GSM1179283 Xpatid_89
GSM1179284 Xpatid_185
This SubSeries is part of SuperSeries:
GSE48462 MGMT-STP27 methylation status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951
BioProject PRJNA210232

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
GSE48461_RAW.tar 183.1 Mb (http)(custom) TAR
GSE48461_non_normalized.txt.gz 190.9 Mb (ftp)(http) TXT
Processed data included within Sample table

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