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
|Contact: Lauren Woods|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College