Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CpG site methylation of HCV-cirrhotic, HCV-HCC, and normal liver tissues

ABSTRACT: In this study we used a high-throughput method for assaying methylation of CpG sites simultaneously in a single sample for identifying differences in methylation observed in tissues ranging from normal liver to pre-neoplastic (cirrhosis) and neoplastic (HCC) states. Since there are important clinical and prognostic differences among HCC patients due to etiology, this study was designed to focus on HCC due to HCV-infection, a more common etiology of HCC among Western countries cross-sectional: 20 cirrhosis, 20 HCC, and 16 normal patients, 87 arrays

ORGANISM(S): Homo sapiens

SUBMITTER: Robert Fisher

PROVIDER: E-GEOD-18081 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma.

Archer Kellie J KJ Mas Valeria R VR Maluf Daniel G DG Fisher Robert A RA

Molecular genetics and genomics : MGG 20100218 4

Methylation of promoter CpG islands has been associated with gene silencing and demonstrated to lead to chromosomal instability. Therefore, some postulate that aberrantly methylated CpG regions may be important biomarkers indicative of cancer development. In this study we used the Illumina GoldenGate Methylation BeadArray Cancer Panel I for simultaneously profiling methylation of 1,505 CpG sites in order to identify methylation differences in 76 liver tissues ranging from normal to pre-neoplasti ...[more]

PMID: 20165882

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Project description:Integrated profiling of somatic molecular alterations present in tumors is necessary to further our understanding of the tumorigenic process. We investigated the potential relationships between gene copy number alterations and DNA methylation profiles in a case series of pleural mesotheliomas (n=23). Gene copy number (CN) alterations profiled with 500K SNP arrays and DNA methylation measured at over 750 cancer-related genes with methylation bead-arrays were examined concomitantly. Considering each probed locus, there were no instances of significantly correlated CN alteration and methylation (no loci with Q < 0.05) and averaging loci over their associated genes revealed only two genes with significantly correlated CN and methylation alterations (Q < 0.04). In contrast to the lack of discrete correlations, the overall extent of tumor CN alteration was significantly associated with DNA methylation profile when comparing CN alteration extent among methylation profile classes (P < 0.02), and there was evidence that this association was partially attributable to prevalent allele loss observed at the maintenance DNA methyltransferase DNMT1. Taken together, this work indicates a strong association between global genetic and global epigenetic dysregulation in mesothelioma rather than a discrete, local coordination of gene inactivation, and further highlights the utility and necessity of integrative genomics approaches in cancer biology. Mesotheliomas were obtained following surgical resection at Brigham and Women’s Hospital through the International Mesothelioma Program from a pilot study conducted in 2002 and an incident case series beginning in 2005 as previously described (PMIDs: 19118007 and 19638575). All patients provided informed consent under the approval of the appropriate Institutional Review Boards. Clinical information, including histologic diagnosis was obtained from pathology reports. The study pathologist confirmed the histologic diagnoses and further assessed the percent tumor from resected specimens (mean >60%). DNA extraction and methylation analysis: DNA from fresh frozen tissue and matched whole blood was isolated with QIAamp DNA mini kit (Qiagen, Valencia, CA) following the manufacturer’s protocol. Tumor DNA was modified with sodium bisulfite using the EZ DNA Methylation Kit (Zymo Research, Orange, CA). Illumina GoldenGate® methylation bead arrays interrogated 1505 CpG loci associated with 803 cancer-related genes processed at the UCSF Institute for Human Genetics, Genomics Core Facility using methods described in (28). The GoldenGate methylation data used in the analysis has been previously described (PMIDs: 19118007 and 19638575).

Dataset Information

CpG site methylation of HCV-cirrhotic, HCV-HCC, and normal liver tissues

Publications

High-throughput assessment of CpG site methylation for distinguishing between HCV-cirrhosis and HCV-associated hepatocellular carcinoma.

Similar Datasets

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