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Cancer epigenetics takes center stage - 1 views

www.pnas.org/...392.full

shared by chanon chiarnpattanodom on 16 Apr 12 - No Cached

- chanon chiarnpattanodom on 16 Apr 12
  
  DNA methylation is a chemical process where a methyl group is added on either the cytosine ring or the adenine ring, used in "higher leveled" organisms. Important in cell differentiation since methylation will cause cells to "remember" and remain differenciated instead of expressing other genes.
  
  <div class="cArrow"> </div><div class="cContentInner">DNA methylation is a chemical process where a methyl group is added on either the cytosine ring or the adenine ring, used in "higher leveled" organisms. Important in cell differentiation since methylation will cause cells to "remember" and remain differenciated instead of expressing other genes. </div>
  
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Epigenetics is defined as modifications of the genome, heritable during cell division, that do not involve a change in the DNA sequence.
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Epigenetic alterations in cancer include global hypomethylation
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the promoters of housekeeping genes that are generally protected from methylation.
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may lead to aberrant silencing of tumor suppressor genes
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discovered loss of imprinting (LOI) in cancer
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Genomic imprinting, the subject of the report by Nakagawa et al. (2), is an epigenetic modification of a specific parental allele of a gene, or the chromosome on which it resides, in the gamete or zygote, leading to differential expression of the two alleles of the gene in somatic cells of the offspring.
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we found that LOI can occur in the normal colonic mucosa of colorectal cancer patients with LOI in their tumors
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This LOI was linked to cases showing microsatellite instability (MSI) in the tumors
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However, these patients do not have mutations in mismatch repair genes
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One potential cause of MSI in these sporadic cancers is hypermethylation and epigenetic silencing of the hMLH1 mismatch repair gene
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Nakagawa et al. (2) now confirm the original study of Cui et al. that LOI occurs in both tumor and normal tissue of patients
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The present study (2) also offers an intriguing mechanistic hypothesis to explain the relationship between H19 DMR methylation and LOI in these patients
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Nevertheless, the study calls attention to this remarkable highly conserved multifunctional protein,
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The potential link to CTCF suggested by this study also calls our attention to the link among DNA methylation, epigenetics, and chromatin.
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A clue to the link between MSI and epigenetics may be provided by another sometimes overlooked common thread in epigenetics, namely DNA replication
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repeat-induced gene silencing is thought to be propagated through hemimethylated intermediates during DNA replication
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The studies of Cui et al. (11), Nishihara et al. (20), and Nakagawa et al. (2) suggest a new and provocative view of the timing of epigenetic changes in cancer.
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Studies of transgenic mice with constitutive biallelic expression of IGF2, comparable to LOI, show reduced apoptosis and increased tumor formation
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I conclude by noting that the distinction between cancer genetics and epigenetics has blurred considerably in recent years
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Many conventional “genetic” mechanisms directly affect proteins that regulate chromatin,
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