Meningioma and schwannoma are intracranial nervous system tumors that are predominantly benign in behavior arise through mutation and loss of function in the Neurofibromatosis type 2 (NF2) gene. Meningioma is the most common primary brain tumor and has a variable risk of local recurrence.Our recent work, has identified methylation and genomic signatures of adult schwannomas, meningiomas and radiation induced meningiomas. Moreover, Dr. Aldape’s group has validated that methylation profiling may be better than current clinical parameters in predicting time to recurrence and unfavorable meningioma subgroups in adults. Schwannomas are even rarer in the pediatric population and are benign tumors that can arise from any nerve in the body, most commonly from Cranial Nerve 8. Our previous work has identified that vestibular and spinal schwannomas with bone erosion have distinct methylation signatures.
Meningioma and Schwannoma are far more commonly diagnosed in adults than children. Typically, pediatric meningiomas and schwannomas are thought to be more likely associated with genetic disorders such as neurofibromatosis type 2 (NF-2), Gorlin syndrome, or Rubenstein-Taybi syndrome. With respect to pediatric schwannomas, the epigenetic landscape has never been explored and understanding how it compares to the adult epigenetic landscape may yield new insights. It also remains to be determined and whether methylation signatures correlate with any clinical or pathological features. Therefore, the molecular classification and its relationship with clinicopathological features are understudied in both pediatric meningiomas and pediatric schwannomas. Therefore, there is an urgent need to better understand the epigenetic landscape and biology of these tumors in order to find effective therapeutic strategies. Pediatric meningioma carries a substantial risk of local recurrence. While pediatric schwannomas are not lethal, they exhibit a multitude of morbidities including hearing loss, tinnitus, vertigo and facial palsy. We hypothesize that pediatric meningiomas and schwannomas have unique DNA methylation patterns compared to their adult counterparts that could be used to stratify patient management better or identify novel therapeutic strategies.
What are the goals of this project?
This project aims to determine the epigenetic landscape of pediatric meningiomas and schwannomas using the Infinium MethylationEPIC BeadChip, determine the global copy number alterations in pediatric meningioma and schwannomas and compare the epigenetic and copy number landscape of these tumors to their adult counterparts.
What is the impact of this project?
Evidence from glioma and medulloblastoma support that pediatric tumors are unique from their adult counterparts. Therefore, therapies that may work in adults may not work in children. The methylation profiles of pediatric meningioma and schwannomas with clinical annotation will allow for a comprehensive analysis of pediatric meningiomas and may identify novel targeted therapies or predict which patients may be susceptible to local recurrence.
Why the CBTN request is important to this project?
Accessing the CBTN samples will allow an unprecedented epigenetic analysis of pediatric meningiomas. and schwannomas. Using integrative methylation profiling we will conclusively address how pediatric meningiomas and schwannomas are both similar or unique from their adult counterparts. This project can only be completed with the use of CBTN samples.
The Children's Brain Tumor Network contributed to this project by providing DNA samples.
Dr. Kenneth D. Aldape
Dr. Gelareh Zadeh
Sameer Agnihotri, PhD
Sameer Agnihotri, PhD, joined the faculty of the Department of Neurological Surgery at UPMC Children’s Hospital of Pittsburgh in November of 2016.Dr. Agnihotri graduated from the University of Toronto in 2005 with a bachelor of science honors degree in biology, specializing in genetics. He
UPMC Children's Hospital of Pittsburgh
Ian Pollack, MD
Ian Pollack, MD, is chief of pediatric neurosurgery at UPMC Children’s Hospital of Pittsburgh, A. Leland Albright Professor of Neurosurgery at the University of Pittsburgh School of Medicine, and co-director of the Neurosu
UPMC Children's Hospital of Pittsburgh
Javad Nazarian, PhD, MSc
I am an investigator at the Center for Genetic Medicine in Children’s National Hospital in Washington, D.C., and an assistant professor in Integrative Systems Biology at the George Washington University. I received my PhD from the George Washington University in Genetics in 2005. My dissertation
Children’s National Hospital
Schwannoma is a rare type of tumor that forms in the nervous system. Schwannoma grows from cells called Schwann cells. Schwann cells protect and support the nerve cells of the nervous system. Schwannoma tumors are often benign, which means they are not cancer. But, in rare cases, they can become