UNC Lineberger researchers led by Ian J. Davis, MD, PhD, reported in the journal Cell Reports that they found that stem cells important to bone growth have a characteristic DNA structure that they believe makes them vulnerable to the harmful effects of the genetic abnormality that occurs in Ewing sarcoma.
A discovery by University of North Carolina Lineberger Comprehensive Cancer Center researchers may help explain why a rare cancer occurs more commonly in the children and teenagers.
Ewing sarcoma is a cancer of bones and soft tissue that occurs most frequently in adolescence, when teens typically experience explosive growth. Researchers have known that a genetic abnormality occurs commonly in this type of cancer, and helps to drive the disease. But why does the genetic abnormality cause cancer in cells in the bone and soft tissue, and in adolescence?
In a new study, UNC Lineberger researchers report the answer may lie in the “cell of origin” that has been theorized to go on to develop into this type of cancer. The researchers’ findings, published in Cell Reports, show that stem cells important to bone growth have a characteristic DNA structure that they believe makes them vulnerable to the harmful effects of the genetic abnormality that occurs in Ewing sarcoma. And the cancer and stem cells share a strikingly similar structure at specific repeating DNA sequences, they report.
“This study gets at the question of: Why do some cancers develop in children and young adults, and other cancers develop in older adults?” said the study’s senior author Ian J. Davis, MD, PhD, a researcher at UNC Lineberger and the Denman Hammond Associate Professor in Childhood Cancer in the UNC School of Medicine. “We draw a direct link between a stem cell population and its genomic state, and the development of this specific type of cancer.”
The researchers’ findings point to development of the cancer from mesenchymal stem cells, which are a specific type of undifferentiated stem cell that can go on to produce other types of cells such as bone, fat cells and cartilage. These cells must proliferate to create cells that can generate new bone in growing teens.
“When kids are growing, stem cells need to grow too, and those stem cells turn into bone cells and cartilage cells,” Davis said. “Stem cell growth probably peaks around adolescence and may slow in adulthood.”
The researchers found a similar vulnerability in Ewing sarcoma and mesenchymal stem cells that may make them more susceptible to cancer.
Specifically, they studied the way that repetitive sequences of DNA interact with a class of proteins called histones, which act like a spool around which DNA is wrapped, in both cancer and stem cells. They found that the way DNA is wrapped around histones at these repetitive sequences in Ewing sarcoma bore a striking similarity to that of stem cells. They believe that the “looseness” in the way that DNA and histones interact in stem cells and cancer cells at these repeat sites allows the oncoprotein to interact with the DNA, changing the way that many genes are expressed and helping to drive the cancer.
”This is one way we think the oncogene capitalizes on a pre-existing environment and offers some insight into why the cancer might have a very specific window during which it could develop,” Davis said. “It’s kind of like a seed and soil relationship. The oncoprotein ‘seed’ can only form cancer in the correct stem cell ‘soil.’”