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Scientists unravel role of fusion gene in prostate cancer
Date:5/22/2012

into the chromatin bundle so that it can fit inside a cell's nucleus, and when genes need to be expressed, the chromatin opens up a bit, allowing transcription. Emerging evidence suggests that, within this package, the genome organizes itself according to a non-randomly-assembled, 3-D architecture of hubs and domains that affect when and where individual genes are turned on.

This study shows the oncogenic ERG protein, produced by the ETS prostate cancer fusion gene, binds to specific sites in the genome, which then forces the 3-D genome architecture to vastly change, creating different hubs and domains, Dr. Rickman says. This results in additional chromosomal translocations, as well as a coordinated expression of genes known to be relevant to aggressive prostate cancer, he says.

The research shows just how complex genetic regulation really is and how distortions in this process can lead to cancer, says Dr. Rubin, who is also a professor of pathology and laboratory medicine and professor of pathology in urology at Weill Cornell Medical College.

"We used to think everything related to gene expression was linear, that one promoter affected the gene located right next to it," he says. "Now we are beginning to understand that what happens in the 3-D space of tightly bundled DNA is also important -- how DNA opens up and undergoes changes that efficiently turn on whole sets of genes that aren't located anywhere near each other."

It Takes a Village -- of Scientists

Reaching these findings required a collaborative team of scientists, says Dr. Rubin, who co-discovered the ETS fusion gene. For this project, he sought the expertise of Dr. Rickman and Dr. Olivier Elemento, an assistant professor in the Department of Physiology and Biophysics and assistant professor of computational genomics in the Institute for Computational Biomedicine at Weill Cornell Medical College, and a co-senior author of the paper. Dr. Elemento and h
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Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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