Epigenetics Affects Cancer

The study of epigenetic mechanisms in cancer, such as DNA methylation, histone modifications, nucleosome positioning and micro-RNA expression, has revealed a plethora of events that contribute to the neoplastic phenotype through stable changes in the expression of genes critical to transformation pathways. [17]

"Quantum dots spot epigenetic markers for early cancer detection"

" The nanotechnology based test for epigenetic markers could be used as an early detection method for cancer or to determine whether a particular cancer treatments is working or not. The research was performed by INBT affiliated faculty member Jeff Tza-Huei Wang, an associate professor of mechanical engineering from the Whiting School of Engineering, and Stephen Baylin, deputy director of the Johns Hopkins Kimmel Cancer Center." [2]

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Mechanisms of Epigenetic Gene Silencing

Epigenetic alterations are useful not only as therapeutic targets, but also in determining patient prognosis and predicting response to therapy. Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene, which encodes a DNA-repair enzyme, inhibits the killing of tumor cells by alkylating agents. Studies have shown that methylation of the MGMT promoter in patient glioma samples is a useful predictor of the responsiveness of the tumors to alkylating agents. When this gene is silenced by methylation, patients are likely to have a better outcome after therapy. The effects of gene silencing on tumor formation and growth can therefore be both positive and negative. [20]








The picture above is a ying-yang of how epigenetics affects cancer. Loss of imprinting might be caused by genetic disruption of CTCF or by altered methylation of the DMR (illustrated). Other examples of overlap or in which the distinction between genetics and epigenetics are blurred are provided in the text. [18]

 The picture on the left is that of a DNA mutation leads to cellular transformation, but induced changes in the epigenome of the transformed cell enhances the probability that it will be capable of metastasisine.  In this scenario, a genetic mutation initiates the cancer but epigenetic change promotes its progression. [19]

Cancer Cells and Epigenetics 101

"In cancer cells, genes are either modified by mutations, which alter the function of the proteins they encode, or through epigenetics -- modifications to chromosomes that alter gene-expression patterns. This can occur through DNA methylation, and methylation, acetylation, or phosphorylation of histones and other proteins around which DNA is wound to form chromatin". [21]

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