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Epigenetic Targets in Cancer research

A New Study on Epigenetic Changes in Cancer Development

By KARI BURNS
    In humans, DNA encodes roughly 25,000 genes. Epigenetic changes such as DNA methylation, histone modification or post-transcriptional silencing through micro RNAs control how these genes can be accessed by proteins involved in gene transcription and therefore influence how these genes are expressed. 
    Seema Singhal and Jayesh Mehta, both physicians at Northwestern Memorial Faculty Foundation, are among the authors of a recent study that investigates how epigenetic changes, namely DNA methylation, can influence the pathogenesis of multiple myeloma. Multiple myeloma is an incurable blood cancer affecting roughly 63,000 people in the USA. Approximately 20,000 new cases are diagnosed each year in the United States. Multiple myeloma accounts for 15 percent of all hematologic cancers and 2 percent of all cancers in the U.S. 
    Gene transcription and expression is regulated by epigenetic mechanisms among others. Hypermethylation of a gene for instance, can lead to underexpression or suppression of expression of this particular gene. Conversely hypomethylation of a gene can lead to its increased expression. Hyper- and hypo-methylation are part of an intricate system which controls normal cell function and aids in the suppression of genes that can cause cancer and augments the expression of genes that protect against cancer. Disturbance of this methylation code can have devastating consequences and, in fact, abnormal hyper- and hypomethylation have been associated with cancer development through aberrant suppression of tumor suppressor genes, expression of oncogenes, and chromosomal instability.
   In the recently published article in WIREs Systems Biology and Medicine (John Wiley & Sons, Inc), the physicians discuss how epigenetic changes can lead to cancer. Other authors involved in this study are Amy Sharma, Christoph Heuck, Melissa Fazzari, John Greally and Amit Verma.
    Until recently, analysis of DNA methylation was only examined for individual genes. In multiple myeloma very few of the analyzed genes appeared to be involved in the pathogenesis of this disease. The authors describe the first genome-wide analysis of DNA methylation in multiple myeloma. In the published study they found widespread abnormal DNA methylation in myeloma cells when they were compared to their normal counterparts.
     The authors hypothesize that epigenetic changes causing altered protein and gene expression contribute to the pathogenesis of multiple myeloma. Inhibition of the abnormal methylation of DNA through the blockade of DNA methyltransferases offer a new therapeutic angle for the treatment of cancer.
    The good news in this study is that the investigation of DNA methylation changes in the pathogenesis of the blood cancer can provide a model for future system studies of epigenomic dysregulation in cancers.
    Future investigations and a genome-wide analysis of DNA methylation will hopefully reveal new epigenetic targets in cancer research.     
     Cytosine methylation is only but one of many epigenetic and transcriptional systems involved in dysregulated cells. Recently micro RNAs (miRNAs) were found to be associated with cancer. In cancer, the miRNAs are rearranged, amplified or deleted causing abnormal gene expression.
     The authors of the paper say it is therefore necessary to study the whole biological system of the regulatory mechanisms within the genome, not individually, to understand the pathogenesis of cancer.


Published: October 10, 2010
Issue: November 2010 Arts and Politics Issue

Comments

Epigenetic Changes in Cancer Development
This article is in a weekend insert. Who do you think is reading this? After 30 minutes with a medical dictionary I think I have a general understanding. I would reconsider your writing style; maybe write so others can understand as opposed to being impressed what you've learned.
Eddie Snyder, Oct-17-2010