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Title: Intrinsic glioma subtypes in EORTC 26951 (part 6)      
dateReleased:
02-01-2013
description:
Background: Intrinsic glioma subtypes (IGS) are molecularly similar tumors that can be identified based on unsupervised gene-expression analysis. Here, we have evaluated the clinical relevance of these subtypes within EORTC26951, a randomized phase III clinical trial investigating adjuvant procarbazine, CCNU (lomustine) and vincristine (PCV) chemotherapy in anaplastic oligodendroglial tumors. Our study is the first to include gene-expression profiles of formalin-fixed and paraffin-embedded (FFPE) clinical trial samples. Methods: Gene-expression profiling was performed in 140 samples: 47 fresh frozen and 93 FFPE, on HU133_Plus_2.0 and HuEx_1.0_st arrays (Affymetrix), respectively. Results: All previously identified six intrinsic glioma subtypes are present in EORTC26951. This confirms that different molecular subtypes are present within a well-defined histological subtype. Intrinsic subtypes are highly prognostic for overall- (OS) and progression-free survival (PFS). They are prognostic for PFS independent of clinical (age, performance, tumor location), molecular (1p19qLOH, IDH1 mutation, MGMT methylation) and histological parameters. Combining known molecular (1p19LOH, IDH1) prognostic parameters with intrinsic subtypes improves outcome prediction (Proportion of Explained Variation 30% v 23%). Specific genetic changes (IDH1, 1p19qLOH and EGFR amplification) segregate into different subtypes. We identified one subtype, IGS-9 (characterized by a high percentage of 1p19qLOH and IDH1 mutations), that especially benefits from PCV chemotherapy. Median OS in this subtype was 5.5 years after radiotherapy (RT) alone v 12.8 years after RT/PCV; P=0.0349; HR 2.18, 95% CI [1.06, 4.50]. Conclusion: Intrinsic subtypes are highly prognostic in EORTC26951 and improve outcome prediction when combined with other prognostic factors. Tumors assigned to IGS-9 benefit from adjuvant PCV A total of 140 samples were included in this study, profiles of 95 were FFPE derived samples run on exon arrays. 12 samples (part 2) can also be found in GSE16011 (PMID 19920198 and 16357140), and 6 from Oncomine (part 3).
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-43353
refinement:
raw
alternateIdentifiers:
43353
keywords:
functional genomics
dateModified:
06-02-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-14951
name:
Illumina HumanHT-12 WG-DASL V4.0 R2 expression beadchip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-43353/E-GEOD-43353.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-43353/E-GEOD-43353.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE43353
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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