Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Stability of the CpG island methylator phenotype during glioblastoma progression.

ABSTRACT: The Illumina HumanMethylation 450 BeadChip was used on 20 matched pairs of early and late secondary gliomas to assess the changes in DNA methylation during progression. Bisulphite converted DNA from the 40 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

ORGANISM(S): Homo sapiens

SUBMITTER: Farida Latif

PROVIDER: E-GEOD-58298 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Stability of the CpG island methylator phenotype during glioma progression and identification of methylated loci in secondary glioblastomas.

Hill Victoria K VK Shinawi Thoraia T Ricketts Christopher J CJ Krex Dietmar D Schackert Gabriele G Bauer Julien J Wei Wenbin W Cruickshank Garth G Maher Eamonn R ER Latif Farida F

BMC cancer 20140710

<h4>Background</h4>Grade IV glioblastomas exist in two forms, primary (de novo) glioblastomas (pGBM) that arise without precursor lesions, and the less common secondary glioblastomas (sGBM) which develop from earlier lower grade lesions. Genetic heterogeneity between pGBM and sGBM has been documented as have differences in the methylation of individual genes. A hypermethylator phenotype in grade IV GBMs is now well documented however there has been little comparison between global methylation pr ...[more]

PMID: 25012071

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Project description:We analyzed 28 fresh frozen samples from pure SCLC patients and 13 noncancerous lung tissues, using the Illumina Infinium 27k Human DNA methylation Beadchip v1.2 Background: Small cell lung cancer (SCLC) accounts for 13-15% of new lung cancer cases in worldwide and has the poor therapeutic outcomes with a median survival of just over one year. A CpG island methylate phenotype (CIMP) is well known as a methylator phenotype with characteristic promoter DNA methylation alterations, in colorectal cancers, glioblastoma and breast cancers, although there has been no report about any CIMP of SCLC. We investigated whether DNA methylation profiles can provide useful molecular subtyping of SCLC in terms of etiology and prognosis of SCLC. Results: We selected a total of 1741 most differentially methylated CpG sites (s.d. > 0.20) across the 28 SCLC tumor tissues in each DNA methylation platform, after an elimination of the probes related with the X- and Y- chromosome. Unsupervised hierarchical clustering of methylation data from SCLC samples reveals two major subgroups with different prognosis: the 5 years disease-free interval (DFI) rate of patients in cluster 1 (11.1%) was lower than that of patients in cluster 2 (61.57%) (p = 0.001). By multivariate analysis for DFI, both postoperative chemotherapy and cluster 1 were a significant prognostic factor (p = 0.002 and 0.002; respectively). Next, among 1220 genes with methylation and expression data both available, the CpG sites were ranked on the basis of the spearman’s correlation coefficient between cluster 1 and cluster 2 into an ascending order. Finally, we identified that fifty-five CpG sites were nagetively correlated and found that apoptosis pathway was a most differentially expressed. Conclusion: By comprehensive DNA methylation profiling, two distinct subgroups with different molecular and clinical phenotype were identified to evoke a CIMP of SCLC. We found some promoter markers in the apoptosis pathway could make a difference between the two groups, and we hope that our data can contribute to provide a useful resource for the construction of therapeutic strategy and the development of a new chemotherapeutic agent. After genomic DNA was treated with sodium bisulfite, bisulfite-converted genomic DNA was analyzed using Illumina’s Infinium HumanMethylation27 BeadChip.

Dataset Information

Stability of the CpG island methylator phenotype during glioblastoma progression.

Publications

Stability of the CpG island methylator phenotype during glioma progression and identification of methylated loci in secondary glioblastomas.

Similar Datasets

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