Researchers have identified a genetic mutation in brain cancer tumor cells that plays a role in both the growth and the death of the cell. Additionally, the mutation to the newly identified gene may also contribute to the tumor’s resistance to radiation.
The findings, published in Nature Genetics (2014; doi:10.1038/ng.2995), provide both immediate and long-term benefits. Knowing that this mutation may render radiation ineffective, patients could be spared that therapy. The mutation would also serve as a strong candidate for drug development.
The researchers, who collaborated between Duke Medicine in Durham, North Carolina, and China, conducted genetic tests and found that many of the tumor cells had a mutation in the PPM1D gene, which causes cells to proliferate and avoid natural death. This is the first time the mutation was found to be a major driving force in the development of brainstem gliomas; it is not evident in other brain tumors. Brainstem gliomas are a rare and deadly form of childhood and young adult brain cancer.
If tumors have this PPM1D mutation, they do not have another more common genetic mutation to the TP53 gene, a tumor suppressor that, when defective, is linked to half of all cancers.
“This finding has immediate clinical applications, because either mutation—PPM1D or TP53—cause the tumor cells to be resistant to radiation,” said senior author Hai Yan, MD, PhD, a professor of pathology at Duke University School of Medicine. “Knowing that could spare patients from an ineffective treatment approach.”
Additionally, the PPM1D genetic mutation is a strong candidate for new drug development.
“This finding gives us a clue as to why these particular tumors are growing inappropriately,” said co-author Zachary Reitman, MD, PhD, a research associate at Duke. “These clues may help us to design better treatments for this type of cancer.”
Yan said his lab is working to identify new treatments that could target the PPM1D genetic mutation and shut down its cancer-growing capabilities.
“PPM1D is itself a target for drug development, because the gene mutation causes cells to avoid death and proliferate,” Yan said. “In drug development, it’s easier to turn that growth function off than it is to switch on the cell’s defective tumor suppression mechanism.”