DNA Methylation and cancer

Ch, Spruck; Wm, Rideout; Pa, Jones

doi:10.1007/978-3-0348-9118-9_22

Cited by 27 publications

(9 citation statements)

References 122 publications

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“…It has been previously observed that a variety of tumor-derived cell lines feature abnormal, and frequently decreased DNA methylation (Spruck et al, 1993). Although most of the studied cytosines in C6 cells are less methylated than in oligodendrocytes, the +94/+96 Hhal sites are fully methylated.…”

Section: Resultsmentioning

confidence: 98%

Differentiation‐specific demethylation of myelin associated glycoprotein gene in cultured oligodendrocytes

Grubinska

Laszkiewicz

Royland

et al. 1994

J of Neuroscience Research

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The methylation status of a 4.4-kb 5' end of the myelin-associated glycoprotein (MAG) gene was assessed in cells with different levels of transcriptional activity of the gene, i.e., liver, brain, O-2A oligodendrocyte precursors cells, mature oligodendrocytes, and glioma C6 cells. Purified DNA was digested with methylation-sensitive restriction enzymes, and the cuts were mapped by the indirect end-labeling technique. The restriction sites within the 4.4-kb fragment revealed a highly heterogenous methylation pattern among cells and tissues, and liver DNA was the most heavily methylated. Most of the restriction sites were partly demethylated in the nervous system cells. Notably, two adjacent Hha1 sites at +94 and +96 were fully methylated in liver, but partially demethylated in the brain, OL, and O2A. Two Hpa2 site located at -1836 and at -39 were progressively demethylated in oligodendrocyte lineage cells, indicating specific hypomethylation associated with the oligodendrocytic differentiation. Most of the restriction sites were weakly methylated in the DNA from neoplastic C6 cells, although the Hha1 sites were fully methylated. No clear-cut correlation between the extent of CpG dinucleotide methylation and the chromatin conformation was found. For example, out of four heavily methylated sites only two comapped with MNase hypersensitive sites. Also, the -1836 Hpa2 site whose demethylation is concomitant with oligodendrocytic differentiation seems to be localized within precisely positioned nucleosomal arrays of the MAG gene chromatin. The results indicate that the MAG gene undergoes progressive demethylation concomitant with the oligodendrocyte differentiation/maturation. However, certain CpG dinucleotides remain heavily methylated even in the fully active gene in mature oligodendrocytes, indicating that they may be essential in maintaining proper chromatin structure.

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Section: Resultsmentioning

confidence: 98%

Differentiation‐specific demethylation of myelin associated glycoprotein gene in cultured oligodendrocytes

Grubinska

Laszkiewicz

Royland

et al. 1994

J of Neuroscience Research

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“…In addition, the CpG islands of these two types of genes also become methylated at a later stage. It may be postulated that the methylation patterns of HOX genes reflect signals established earlier in development possibly modified during the tumoral progression which is often associated with striking DNA methylation modifications (reviewed in [35]). The specific methylation of the HOX genes could be required to distinguish key genes with respect to their function(s) in the network.…”

Section: Discussionmentioning

confidence: 99%

Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers

et al. 1996

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The expression pattern of the HOXB gene cluster in four xenografted small-cell lung cancers was compared to the methylation of the DNA in the corresponding genomic regions. In 90% (17/19) of the studied cases, the expressed genes were in methylated regions whereas 70% (12/17) of the unexpressed genes were in unmethylated regions. This specific behavior could correspond to a particular gene expression regulation mechanism of the HOX gene network. Since some genes (HOXB2, HOXB4, HOXB7) were always inactive when unmethylated, this unexpected relationship might indicate their key function(s) in the HOX gene network.

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“…DNA methylation is essential for normal developmental processes, such as imprinting (6) and X chromosome inactivation (7). Dysregulation of DNA methylation occurs in disease states such as cancer, where promoter CpG island hypermethylation leads to inactivation of tumor suppressor genes (8,9). Thus, many tumor suppressors classically identified through mutation analyses, such as APC (10,11), BRCA1 (12,13), and CDKN2A (14,15), have also been found to be transcriptionally silenced by promoter hypermethylation.…”

Section: Introductionmentioning

confidence: 99%

MBD-isolated Genome Sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome

Serre

Lee

Ting

2009

Nucleic Acids Research

363

290

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DNA methylation is an epigenetic modification involved in both normal developmental processes and disease states through the modulation of gene expression and the maintenance of genomic organization. Conventional methods of DNA methylation analysis, such as bisulfite sequencing, methylation sensitive restriction enzyme digestion and array-based detection techniques, have major limitations that impede high-throughput genome-wide analysis. We describe a novel technique, MBD-isolated Genome Sequencing (MiGS), which combines precipitation of methylated DNA by recombinant methyl-CpG binding domain of MBD2 protein and sequencing of the isolated DNA by a massively parallel sequencer. We utilized MiGS to study three isogenic cancer cell lines with varying degrees of DNA methylation. We successfully detected previously known methylated regions in these cells and identified hundreds of novel methylated regions. This technique is highly specific and sensitive and can be applied to any biological settings to identify differentially methylated regions at the genomic scale.

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DNA Methylation and cancer

Cited by 27 publications

References 122 publications

Differentiation‐specific demethylation of myelin associated glycoprotein gene in cultured oligodendrocytes

Differentiation‐specific demethylation of myelin associated glycoprotein gene in cultured oligodendrocytes

Relationship between DNA methylation and gene expression of the HOXB gene cluster in small cell lung cancers

MBD-isolated Genome Sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome

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