Meningiomas are tumors that form in the central nervous system, and are the most common type of brain and spinal cord tumors. According to the National Institutes of Health, it's estimated that about 25,000 Americans get a new meningioma diagnosis every year. Researchers have now discovered a novel genetic link to a subset of meningiomas. The findings have been reported in Nature Communications.
While many meningiomas can be surgically removed, in many cases this is not possible and the tumor keeps growing. Radiation can help shrink these tumors to some degree, but there is no chemotherapeutic approach to treatment. As such, new treatment options are needed.
Although previous research has found genetic causes for around 80 percent of meningiomas, molecular causes for the remaining 20 percent have been unclear, noted first study author Mark Youngblood, MD, PhD.
In this work, the researchers assessed the genomes of tumor samples from different patients. This revealed a subset of meningiomas with structural damage in their DNA, like broken chromosomes, which led to an increase in activity in a biochemical pathway known as hedgehog. This pathway is closely related to cell differentiation and development. The investigators decided to focus on two genes that were often located close to the structural damage: IHH and SHH, which are both part of the headgehog pathway.
"When we looked at the RNA sequencing data, we found that hedgehog ligand genes IHH and SHH had dramatically increased expression compared to meningiomas that did not have these structural variants, explaining the activation of hedgehog signaling in these cases," Youngblood said.
With a tool called Hi-ChIP, the researchers analyzed the DNA structure. They determined that the disrupted structures of DNA in the tumor cells were leading to an unusual interaction between portions of the genome that aren't usually in contact, causing the observed increase in IHH activity.
This research can help explain the genetic problems underlying one subset of meningiomas that have not been understood before this, noted Youngblood. This research has also provided new insight into how hedgehog signaling can impact meningiomas.
"This is the first time that enhancer hijacking of hedgehog pathway ligands has been demonstrated in any form of cancer, which is interesting because this particular pathway plays such a large role across different types of cancers."
There are already FDA-approved drugs that aim for the hedgehog signaling pathway, and it may be possible to used those drugs in a treatment approach for certain types of meningiomas, said study co-author Professor Amy Heimberger, MD, PhD, vice chair for Research in the Department of Neurological Surgery at Northwestern University, among other appointments.
The study has also illustrated how different grade I meningiomas can be even though they were once thought of as generally the same, added Heimberger.
Sources: Northwestern University, Nature Communications
