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Researchers from the University of Colorado Cancer Center have published a study in the journal PLOS Genetics demonstrating that it isn't just a gene that goes haywire in cancer, but abnormalities in the full epigenome that can alter the genetic expression and therefore cause cancer.
The analogy used to explain the epigenome is that of a musical mixing board--the kind with many dozens of different knobs and level adjusters--which functions to balance the various expressions of genes.
Their analogy extends to the researchers themselves, imagining themselves as sound engineers who might somehow configure the many knobs and levels in order to lower the protein expression of one cancerous gene or turning up their sensitivity to treatments.
Enter methylation, a chief tool of the epigenome. Methylation attaches so-called methyl groups to DNA sequences near the genes in order to silence or promote their expression.
Put another way, methylation patterns predict patient survival. Said University of Colorado Cancer Center investigator Subhajyoti De, PhD:
"Not only do we see more abnormal methylation in non-Hodgkin lymphoma patients than in healthy B-cell populations, but there are three distinct subtypes of the disease in the clinic, each more aggressive than the next. These three clinical trajectories of non-Hodgkin's lymphoma were distinctly marked by their levels of abnormal methylation."
In healthy B-cells, DNA is methylated with consistency, but in cancer the methylation from cancerous B-cell to cancerous B-cell is all over the place. The greater the variance from cancer cell to cancer cell, the greater the aggressiveness of the cancer.
Abnormal methylation can therefore be correlated with cancer and with aggressive behaviors of cancer subtypes.
The issue then becomes, how can you regulate methylation in all cells? Some known drugs can moderate methylation in cells, but it is not yet known whether one of these drugs has the capability to shut down cancer.
"For the last 50 years, the scientific community pushed to identify the genetic drivers of cancer, but now in the past five or six years we've expanded the search into the epigenome as well. We now expect to find that both genetic and epigenetic abnormalities are important for initiation and maintenance of cancer."