University of Michigan research reveals that a deficiency in a key tumor suppressor gene in the brain could cause the most common type of adult brain cancer, called Glioblastoma.
Conducted in mice, the study paves way for more effective future treatments and a way to screen for the disease early.
For the first time, the findings in mice show that Glioblastoma may originate in neural stem cells located in a brain region known as the subventricular zone (SVZ).
Also, the researchers found that in mice, neural stem cells that normally live in this niche give rise to more specialized nerve cells that migrate out of the niche.
Cancer could begin with a single genetic mutation in the p53 gene, which makes stem cells migrate out of the niche like their specialized progenies.
The study has mainly focused on the p53 gene, known as the "guardian of the genome" because it initiates a wave of other gene actions that normally thwart cancer.
Dr. Yuan Zhu, the study's senior author, said that the finding of a specific zone of origin could lead to treatments that might improve the dire median survival rate of 12 months for this type of brain cancer.
Zhu said if glioblastoma originates in neural stem cells in the SVZ in humans as it does in mice, the study suggests that doctors need to direct treatments there, as well as to the tumor, for eliminating the source of the cancer and keep it from returning.
The findings in mice might also lead in time to effective early screening tests for glioblastoma.
The scientists have shown that the expression of mutant p53 protein is a marker for glioma cells in all stages of the disease.
"Now, if we believe that the SVZ is the location of the cells of origin, with enhanced resolution we could detect tumor cells there," said Zhu.
If the disease could be detected early, the chances of treatment success should also improve.
Zhu also said that scientists should carefully proceed with new treatments for neurodegenerative diseases such as Parkinson's disease, where the hope is to use neural stem cells to help regenerate lost nerve function.
He added: "Our results in mice show that these neural stem cells in the brain have high potential to accumulate genetic lesions and to become a cellular target for cancerous cells."
For the study, the researchers conducted a series of experiments using mice engineered to have a p53 mutation in the central nervous system.
They found that a majority developed malignant brain tumors, and that a mutant form of p53 was present in the tumor cells, a phenomenon that is commonly found in human glioblastoma.
The new study specifically reveals that glioblastoma begins in neural stem cells that have a p53 mutation.
Then, the cells give rise to mutated, fast-multiplying cells down the line of cell differentiation, a class called transit-amplifying progenitor cells.
"We found that the cells with p53 mutations are highly plastic. If a treatment blocks one path of action, they may learn other ways to grow," said Zhu.
The study has been published in the journal Cancer Cell.