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Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE25083: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: normal head and neck tissue GSE25089: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: HNSCC GSE25091: Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: blood controls Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Graham Poage

PROVIDER: E-GEOD-25093 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global hypomethylation identifies Loci targeted for hypermethylation in head and neck cancer.

Poage Graham M GM Houseman E Andres EA Christensen Brock C BC Butler Rondi A RA Avissar-Whiting Michele M McClean Michael D MD Waterboer Tim T Pawlita Michael M Marsit Carmen J CJ Kelsey Karl T KT

Clinical cancer research : an official journal of the American Association for Cancer Research 20110419 11

<h4>Purpose</h4>The human epigenome is profoundly altered in cancers, with a characteristic loss of methylation in repetitive regions and concomitant accumulation of gene promoter methylation. The degree to which these processes are coordinated is unclear so we investigated both in head and neck squamous cell carcinomas.<h4>Experimental design</h4>Global methylation was measured using the luminometric methylation assay (LUMA) and pyrosequencing of LINE-1Hs and AluYb8 repetitive elements in a ser ...[more]

PMID: 21505061

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Project description:Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer

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Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: normal head and neck tissue

Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas. The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 18 normal head and neck samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

2011-10-27 | E-GEOD-25083 | biostudies-arrayexpress

Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: HNSCC

Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas (HNSCCs). The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 91 head and neck squamous cell carcinoma samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

2011-10-27 | E-GEOD-25089 | biostudies-arrayexpress

Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer: blood controls

Project description:Genome-wide DNA methylation profiling of head and neck squamous cell carcinomas (HNSCCs). The Illumina Infinium 27k Human DNA methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in fresh-frozen tumor tissues. Samples included 91 tumors from the oralpharynx and larynx, reflecting all stages of disease, 18 normal head and neck National Disease Research Interchange (NDRI) samples, and 213 normal control blood samples. Bisulphite-converted DNA from the 213 control blood samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

2011-10-27 | E-GEOD-25091 | biostudies-arrayexpress

The tumor suppressor gene rap1GAP is silenced by mir-101-mediated EZH2 overexpression in invasive squamous cell carcinoma

Project description:Rap1GAP is a critical tumor suppressor gene that is down-regulated in multiple aggressive cancers such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP down-regulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves EZH2, a histone methyltransferase in head and neck cancers. We further concomitant down-regulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of H3K27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression. OSCC3-siRNA Non-Targeting Vs. siRNA EZH2 with dye-swap, HOK-Adeno CMV Vs. Adeno EZH2.

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The tumor suppressor gene rap1GAP is silenced by mir-101-mediated EZH2 overexpression in invasive squamous cell carcinoma

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Use of the B cell transcription program results in hypomethylation and overexpression of key genes in EBV-mediated conversion of resting to proliferative B cells

Project description:We investigated the effects of experimental EBV infection of B cells on DNA methylation profiles by using high-throughput analysis. Remarkably, we observed hypomethylation of around 250 genes, but no hypermethylation. Hypomethylation did not occur at repetitive sequences, consistent with the absence of genomic instability in lymphoproliferative cells. Changes in methylation only occurred after cell divisions started, without the participation of the active demethylation machinery, and were concomitant with acquisition of B cells of the ability to proliferate. Gene ontology analysis, expression profiling, high-throughput analysis of the presence of transcription factor-binding motifs and occupancy revealed that most genes undergoing hypomethylation are active and display the presence of NFkB p65 and other B cell-specific transcription factors. Promoter hypomethylation associated with upregulation of genes relevant for the phenotype of proliferating lymphoblasts. Interestingly, pharmacologically-induced demethylation increased the efficiency of transformation of resting B cells to lymphoblastoid cells, suggesting the establishment of a productive cooperation between hypomethylation and lymphocyte proliferation. Bisulfite-converted DNA from 12 samples (6 Bcell, 6 Bcell immortalized) were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2.

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