In a new study in PNAS, researchers from Weill Cornell Medical College and their collaborators describe a novel chromosomal arrangement that they say results in a fusion gene that is present in about half of all prostate cancer cells. In a New York-Presbyterian Hospital press release, the researchers say that the chromatin in the cancer cells in wrapped in such a way as to cause several genes to promote abnormal and unchecked cell growth. The ERG protein, which is produced by the ETS fusion gene, forces the chromatin structure to change, resulting in additional chromosomal translocations and the increased expression of genes known to be associated with aggressive prostate cancer.
"These findings … are the first to show how this chromosomal mutation likely contributes to early development of prostate cancer — and suggests a model for how other chromosomal translocations, common to many tumor types, are linked to cancer formation and growth," New York-Presbyterian says. "The study also adds to the growing understanding of how remodeling of the chromatin regulates genes linked to cancer."
The researchers note that studies such as this one add to the scientific community's understanding of the complexity of gene regulation and how that process can go awry to cause cancer to develop. "We used to think everything related to gene expression was linear, that one promoter affected the gene located right next to it," says senior author Mark Rubin. "Now we are beginning to understand that what happens in the 3D 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."