Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The effects of EBV transformation on gene expression and methylation levels

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Minal Caliskan

PROVIDER: E-GEOD-26212 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The effects of EBV transformation on gene expression levels and methylation profiles.

Caliskan Minal M Cusanovich Darren A DA Ober Carole C Gilad Yoav Y

Human molecular genetics 20110202 8

Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of B cells reduce the usef ...[more]

PMID: 21289059

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Project description: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. Bisulphite converted DNA from the 58 samples were hybridised to the Illumina Infinium 27k 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.

Dataset Information

The effects of EBV transformation on gene expression and methylation levels

Publications

The effects of EBV transformation on gene expression levels and methylation profiles.

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