"Some people may still think of these non-coding sequences as junk; that they don't really do anything but act as hangers-on to the more famous parts of the genome," said the study's senior author Ian J. Davis, MD, PHD, a pediatric oncologist and researcher at UNC Lineberger and the Denman Hammond Associate Professor in Childhood Cancer at the UNC School of Medicine. "But we found that repetitive elements contribute to cancer development for Ewing sarcoma based on traits that they share with immature cells."
For most people with Ewing sarcoma, the tumors have a mutation that creates a new gene called EWSR1-FLI1. This gene codes for a mutant protein, called an oncoprotein, that drives the cancer. But it turns out that the mutant protein does not work alone.
UNC Lineberger researchers found that specific states of DNA have enhanced susceptibility to the oncoprotein's attack. In particular, the way that repetitive DNA sequences interact with a class of proteins called histones, which act like a spool around which DNA is wrapped, offer an opportunistic environment for the oncoprotein. At certain sites, the DNA is more "open" or unwrapped around the histone spools, making them more accessible to the oncoprotein.