Study Maps Mutation That May Drive Meningioma Development in Childhood Cancer Survivors

Key Points

  • The team analyzed radiation-induced meningiomas from patients who had received cranial-spinal radiation as children, the majority of whom (74%) had survived either leukemia or pediatric brain cancer.
  • The study also showed that radiation-induced meningiomas developed regardless of the radiation dose by collaborating with scientists in Germany where low-dose radiation was a common treatment many years ago for scalp ringworm.
  • The research identified a specific rearrangement involving the NF2 gene that causes radiation-induced meningiomas.

Neuroscientists may have uncovered the genetic basis for why many long-term survivors of childhood cancer develop meningiomas, the most common adult brain tumor, decades after their treatment with cranial radiation. The findings, published by Agnihotri et al in Nature Communications, show that radiation causes genetic rearrangements in DNA that result in meningiomas, explained co–principal investigators Gelareh Zadeh, MD, PhD, FRCSC, and Kenneth Aldape, MD.

The study compared and contrasted the biology of radiation-induced meningiomas to those that appear sporadically in the general population. “Radiation-induced meningiomas appear the same on [magnetic resonance imaging (MRI)] and pathology, feel the same during surgery, and look the same under the operating microscope. What's different is they are more aggressive, tend to recur in multiples, and invade the brain, causing significant morbidity and limitations (or impairments) for individuals who survive following childhood radiation,” said Dr. Zadeh.

Study Findings

The research team analyzed radiation-induced meningiomas from patients who had received cranial-spinal radiation as children, the majority of whom (74%) had survived either leukemia or pediatric brain cancer. The study also showed that radiation-induced meningiomas developed regardless of the radiation dose by collaborating with scientists in Germany where low-dose radiation was a common treatment many years ago for scalp ringworm.

“By understanding the biology, the goal is to identify a therapeutic strategy that could be implemented early on after childhood radiation to prevent the formation of these tumors in the first place,” said Dr. Zadeh.

Dr. Aldape said, “It is an important clinical problem because it presents a paradoxical dilemma that while cranial-spinal radiation is needed to cure many childhood cancers, an unfortunate consequence is that 10 to 15 years following radiation treatment, some survivors develop meningiomas. Our research identified a specific rearrangement involving the NF2 gene that causes radiation-induced meningiomas. But there are likely other genetic rearrangements that are occurring as a result of that radiation-induced DNA damage. So one of the next steps is to identify what the radiation is doing to the DNA of the meninges.”

He added, “In addition, identifying the subset of childhood cancer patients who are at highest risk to develop meningioma is critical so that they could be followed closely for early detection and management.”

Dr. Zadeh is a neurosurgeon-scientist and Head of Surgical Oncology at the Princess Margaret Cancer Centre, University Health Network, and is also Associate Professor, Division of Neurosurgery, the Wilkins Family Chair in Brain Tumor Research at the University of Toronto. Dr. Aldape is a neuropathologist-scientist and Director of the MacFeeters-Hamilton Neuro-Oncology Research Program at the Princess Margaret Cancer Centre, University Health Network; and is also Professor, Laboratory Medicine and Pathobiology, at the University of Toronto.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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