Comprehensively Characterizing the Schwannoma Genome

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Peleg Horowitz, MD, PhD

Schwannomas are a diverse group of brain tumors that cause symptoms by progressively and unrelentingly compressing and displacing the normal brainstem and cranial nerve anatomy at the skull base. Most schwannomas are slow growing, but their clinical impact on patients isanything but benign: symptoms progress from ringing in the ears, imbalance, and hearing loss to facial dysfunction, brainstem compression, and early death. The intimate relationship of these tumors to nerve fibers controlling facial expression and hearing makes their treatment challenging.

Treatments for many other tumor types have arisen from an understanding of the subtle differences between tumor and normal cells. Particularly important are changes in the genetic code that serve as a blueprint for how cells should behave. Early studies into the genetics of schwannomashave shown frequent disruptions of a gene called NF2 that encodes a tumor suppressor; however, no treatments currently exist that target NF2 directly.

A major barrier to more effective treatments is the lack of understanding of the genetic events outside of NF2 in these tumors. Preliminary findings suggest that other parts of the genome may be important as well. This project will perform an in-depth, comprehensive study of the genomes of several schwannomas to fully characterize the genetic alterations in these tumors. Such changes may be in the form ofsubtle mutations (“typos” in the genetic code), larger deletions or insertions, or even massive genetic rearrangements that give tumor cells a particular growth advantage over normal nerve sheath cells. These findings will then be verified with a focused study of a much larger group of schwannomas. Dr. Horowitz and his team hope that this study will uncover important new genetic changes that drive schwannoma growth and development, pointing the way to new treatment strategies.