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  • The epigenetics of cancer, a recent view

    51The genetic model of cancer has led research in this field for decades, until Feinberg and Vogelstein (Johns Hopkins) described in 1983 an extensive loss of DNA methylation in tumor cells. With the results came the first evidence that epigenetic changes, heritable but outside the sequence, could make the cancer. The manifest skepticism that greeted the idea was in part due to the slow pace of progress in this field over the next fifteen years.

    Epigenetics, while the interlocutor of the environment with genetics, including reversible changes in the DNA-binding proteins that modulate his expression of genes depending on external conditions. Conrad Waddington coined the term in 1942, and defined it as “the branch of biology that studies the causal interactions between genes and their products, which bring the phenotype.” The current definition refers to heritable changes in genome function that occur without a change in the nucleotide sequence of DNA. The importance of this discipline and its consequences are reflected in the recent launch of the Human Epigenome Project Consortium and the creation of the European Network of Excellence for Research on epigenome, whose only laboratory is the Spanish member of the CNIO Maria Blasco.

    With just a decade, this discipline is seen as relevant in cancer research, especially given the evidence in this direction that have emerged in the last five years, and are opening up perspectives for diagnosis, prevention and treatment. Indeed, in February 1999, Nature Genetics published the article “comes the era of cancer epigenetics,” review of the role of DNA methylation in malignancy. The discovery of numerous hyper ethylated promoters of tumor suppressor gene, together with a better understanding of gene silencing, this mechanism gave a role in the inactivation of tumor suppression and, therefore, in the activation of cancer. The authors suggested that the hypothesis of Knudson (requires two mutations, two hits, for its appearance: a recessive inherited from parents and other acquired independently during the first years of life enunciated after study with retinoblastoma, coincidentally the same model used by Ferres et al. at work commented that this section) should be expanded to include epigenetic mechanisms of gene inactivation.

    This is definitely a new vision of cancer, which very significantly large genetic model and opens the door to new and critical approaches. To the extent that it seems already clear that the aberrations in the three major forms of epigenetic programming (DNA methylation, genomic imprinting and histone modification) contribute importantly to this disease. It is therefore considered that cancer arises from the interaction of genetic and epigenetic factors, and it is not possible to address both aspects independently.

    Published on August 14, 2012 · Filed under: Bioscience; Tagged as: , , , ,
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