Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?

@article{Baylin2006EpigeneticGS,
  title={Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?},
  author={Stephen B. Baylin and Joyce Ellen Ohm},
  journal={Nature Reviews Cancer},
  year={2006},
  volume={6},
  pages={107-116}
}
Chromatin alterations have been associated with all stages of tumour formation and progression. The best characterized are epigenetically mediated transcriptional-silencing events that are associated with increases in DNA methylation — particularly at promoter regions of genes that regulate important cell functions. Recent evidence indicates that epigenetic changes might 'addict' cancer cells to altered signal-transduction pathways during the early stages of tumour development. Dependence on… 
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References

SHOWING 1-10 OF 130 REFERENCES
The fundamental role of epigenetic events in cancer
TLDR
This review discusses patterns of DNA methylation and chromatin structure in neoplasia and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.
Cancer-epigenetics comes of age
TLDR
Current mechanistic understanding of the role of DNA methylation in malignant transformation is reviewed, and it is suggested Knudson's two–hit hypothesis should be expanded to include epigenetic mechanisms of gene inactivation.
Epigenetics in human disease and prospects for epigenetic therapy
TLDR
Great potential lies in the development of ‘epigenetic therapies’ — several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.
Gene silencing in cancer in association with promoter hypermethylation.
TLDR
The mechanisms of gene silencing in cancer and clinical applications of this phenomenon are reviewed, especially tumor-suppressor genes.
A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer
TLDR
Using cDNA microarray analysis to screen for genes that are epigenetically silenced in human colorectal cancer shows that this approach can identify a substantial number of genes with promoter hypermethylation in a given cancer; these are distinct from genes with unmethylated promoters, for which increased expression is produced by histone deacetylase inhibition alone.
Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene.
Distinct epigenetic changes in the stromal cells of breast cancers
TLDR
A new method, methylation-specific digital karyotyping, was developed and applied to epithelial and myoepithelial cells, stromal fibroblasts from normal breast tissue, and in situ and invasive breast carcinomas and showed that distinct epigenetic alterations occur in all three cell types during breast tumorigenesis, suggesting that epigenetic changes have a role in the maintenance of the abnormal cellular microenvironment in breast cancer.
DNMT1 and DNMT3b cooperate to silence genes in human cancer cells
TLDR
It is demonstrated that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and compelling evidence that such methylation is essential for optimal neoplastic proliferation is provided.
Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma.
Opposing effects of DNA hypomethylation on intestinal and liver carcinogenesis.
TLDR
Findings support the notion of a dual role for DNA hypomethylation in suppressing later stages of intestinal tumorigenesis, but promoting early lesions in the colon and liver through an LOH mechanism.
...
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