GENETIC CHANGES IN RADIATION-ASSOCIATED MENINGIOMA

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Abstract

BACKGROUND: Meningiomas represent the most frequently diagnosed primary brain tumor in the United States accounting for approximately one third of such tumors in adults. To date the sole consistently identified risk factor remains exposure to ionizing radiation with risks from 6-10 fold reported. Persons diagnosed with meningioma after exposure to therapeutic ionizing radiation likely represent a genetically-sensitive subpopulation of patients. Currently, radiation-associated meningiomas (RAM) are the most common form of radiation-induced neoplasm yet no sequencing data exist for this class of tumor. METHODS: Our group has identified 22 persons with confirmed high-dose therapeutic radiation treatments to the head, face or neck and subsequent pathologic confirmation of intra-cranial meningioma. To identify genetic changes and the mean number of protein altering somatic mutations associated with the development of RAM we perform whole genome sequencing on matched paraffin-embedded tumor and constitutive DNA for this group of patients. We compare these results with those obtained from the recent genetic analyses of two series of non-RAM meningiomas to determine how mutation profiles differ between RAM and non-RAM meningiomas. RESULTS: Treatment is problematic as many RAMs are in anatomic locations that are difficult to surgically access, most patients are not candidates for additional radiation therapy given their previous exposure and no beneficial chemotherapeutic agent exists. (Sequencing in process) CONCLUSIONS: RAMs represent a difficult clinical issue in neurosurgery. Our study is a focused effort to define genetic variants associated with meningioma development using cases with a unique gene*environment exposure. In addition, these data may identify mutational profiles that predict drug response for this hard to treat lesion. SECONDARY CATEGORY: Tumor Biology.

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