Characterizing DNA methylation alterations from The Cancer Genome Atlas

The Journal of clinical investigation (Impact Factor: 13.22). 01/2014; 124(1):17-23. DOI: 10.1172/JCI69740
Source: PubMed


The Cancer Genome Atlas (TCGA) Research Network is an ambitious multi-institutional consortium effort aimed at characterizing sequence, copy number, gene (mRNA) expression, microRNA expression, and DNA methylation alterations in 30 cancer types. TCGA data have become an extraordinary resource for basic, translational, and clinical researchers and have the potential to shape cancer diagnostic and treatment strategies. DNA methylation changes are integral to all aspects of cancer genomics and have been shown to have important associations with gene expression, sequence, and copy number changes. This Review highlights the knowledge gained from DNA methylation alterations in human cancers from TCGA.

57 Reads
  • Source
    • "Integrated analysis of the relationship between DNA methylation and gene expression DNA methylation changes in promoter regions are integral to all aspects of tumorigenesis and have been shown to have important relevance with gene expression (Weisenberger, 2014). Recently, transcriptome profiling has revealed that a significant subset of transcripts longer than 200 nucleotides, located in non-coding regions, known as long non-coding RNAs (lncRNAs), can modulate gene expression, but their DNA methylation patterns remain poorly understood. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Organisms and cells, in response to environmental influences or during development, undergo considerable changes in DNA methylation on a genome-wide scale, which are linked to a variety of biological processes. Using MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively costly. In this study, we develop a novel approach, named MBRidge, to detect the methylation levels of repertoire CpGs, by innovatively introducing C-hydroxylmethylated adapters and bisulfate treatment into the MeDIP-seq protocol and employing ridge regression in data analysis. A systematic evaluation of DNA methylome in a human ovarian cell line T29 showed that MBRidge achieved high correlation (R>0.90) with much less cost (∼10%) in comparison with MethylC-seq. We further applied MBRidge to profiling DNA methylome in T29H, an oncogenic counterpart of T29's. By comparing methylomes of T29H and T29, we identified 131790 differential methylation regions (DMRs), which are mainly enriched in carcinogenesis related pathways. These are substantially differ from 7567 DMRs that were obtained by RRBS and related with cell development or differentiation. The integrated analysis of DMRs in the promoter and expression of DMR-corresponding genes revealed that DNA methylation enforced reverse regulation of gene expression, depending on the distance from the proximal DMR to transcription starting sites in both mRNA and lncRNA. Taken together, our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.
    Journal of Molecular Cell Biology 06/2015; 7(4). DOI:10.1093/jmcb/mjv037 · 6.77 Impact Factor
  • Source
    • "Histone acetylation is associated with gene expression while methylation and de-acetylation are associated with gene silencing. Similarly , DNA methylation is associated with gene silencing and is the most studied of the epigenetic processes, especially in the field of cancer research (Subramaniam et al., 2014; Weisenberger 2014). However, relatively little is known of the role epigenetics plays in the progression and development of periodontal diseases (Lod et al., 2013; Barros and Offenbacher 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic modifications are changes in gene expression without altering DNA sequence. We previously reported that bacteria-specific innate immune responses are regulated by epigenetic modifications. Our hypothesis is that DNA methylation affects gingival cytokine secretion in response to bacterial stimulation. Gingival epithelial cells (GECs) were treated with DNMT-1 inhibitors prior to Porphyromonas gingivalis (Pg) or Fusobacterium nucleatum (Fn) exposure. Protein secretion was assessed using ELISA. Gene expression was quantified using qRT-PCR. The ability of bacteria to invade inhibitor pretreated GECs was assessed utilizing flow cytometry. Changes were compared to unstimulated GECs. GEC upregulation of IL-6 and CXCL1 by Pg or Fn stimulation was significantly diminished by inhibitor pretreatment. Pg stimulated IL-1α secretion and inhibitor pretreatment significantly enhanced this upregulation, while Fn alone or with inhibitor pretreatment had no effect on IL-1α expression. GEC upregulation of human beta-definsin-2 in response to Pg and Fn exposure was enhanced following the inhibitor pretreatment. GEC susceptibility to bacterial invasion was unaltered. These results suggest that DNA methylation differentially affects gingival cytokine secretion in response to Pg or Fn. Our data provide basis for better understanding of how epigenetic modifications, brought on by exposure to oral bacteria, will subsequently affect host susceptibility to oral diseases. © FEMS 2014. All rights reserved. For permissions, please e-mail:
    Pathogens and Disease 12/2014; 73(2). DOI:10.1093/femspd/ftu005 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The field of epigenetics has exploded in the last two decades, with incredible advances in recent years driven by high-throughput sequencing studies. Cancer cells frequently exhibit marked changes in DNA methylation and histone modification during tumorigenesis and tumor progression. These changes in the cancer epigenome are thought to be important in initiating and maintaining malignancy, and pharmaceutical approaches targeting epigenome-modifying enzymes are an attractive therapeutic strategy. Early successes have been made with DNA-demethylating drugs in hematologic malignancies, and efforts are underway to target additional epigenetic regulators and a broader array of tumor types. The Reviews in this issue of the JCI highlight ongoing efforts in this burgeoning field to translate our understanding of the cancer epigenome into successful interventional strategies in the clinic.
    The Journal of clinical investigation 01/2014; 124(1):14-6. DOI:10.1172/JCI74145 · 13.22 Impact Factor
Show more

Similar Publications