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Epigenomic abnormalities predict patient survival in non-Hodgkins lymphoma
Date:1/10/2013

Think of the epigenome like a giant musical mixing board, turning up or down the expression of various genes. A University of Colorado Cancer Center study published today in the journal PLOS Genetics shows that in cancer, not only can genes themselves go bad, but abnormal changes in the epigenetic mixing board can unfortunately change the expression of these genes. Researchers hope to play the role of sound engineers, controlling these harmful epigenomic changes to turn down cancer itself or perhaps sensitize cancers to existing drugs.

The epigenome's primary tool and by far the easiest to study is methylation: it attaches little methyl groups to DNA sequences near the genes to silence or promote their expression.

"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-Hodgkins lymphoma were distinctly marked by their levels of abnormal methylation," says Subhajyoti De, PhD, CU Cancer Center investigator and assistant professor at the CU School of Medicine.

In other words, methylation patterns predict patient survival. Here's how it works:

DNA should be methylated in a consistent way you get a certain, standardized amount of methyl "residue" attached to your genes. Sure enough, that's the case in healthy B-cells. Subhajyoti and colleagues show that in cancerous B-cells, the level of DNA methylation from cell to cell varies wildly. And the more wildly the level of DNA methylation varies, the more aggressive is the cancer. It's as if, in the body, you want a consistent epigenome that maintains the methylation of the healthy status quo when a willy-nilly epigenome drops methylation randomly here and there, it promotes non-normal cells, like cancer.

So abnormal methylation is certainly correlated with not onl
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Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

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