A mechanistic mathematical model of initiation and malignant transformation in sporadic vestibular schwannoma |
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| Authors: | Chay Paterson Ivana Bozic Miriam J. Smith Xanthe Hoad D. Gareth R. Evans |
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| Affiliation: | 1.Division of Evolution, Infection and Genomics, School of Biological Sciences, University of Manchester, Manchester, UK ;2.Department of Applied Mathematics, University of Washington, Seattle, WA USA ;3.Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK ;4.Radiation Protection Group, Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, UK |
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| Abstract: | ![]()
Background A vestibular schwannoma (VS) is a relatively rare, benign tumour of the eighth cranial nerve, often involving alterations to the gene NF2. Previous mathematical models of schwannoma incidence have not attempted to account for alterations in specific genes, and could not distinguish between nonsense mutations and loss of heterozygosity (LOH).Methods Here, we present a mechanistic approach to modelling initiation and malignant transformation in schwannoma. Each parameter is associated with a specific gene or mechanism operative in Schwann cells, and can be determined by combining incidence data with empirical frequencies of pathogenic variants and LOH.Results This results in new estimates for the base-pair mutation rate u = 4.48 × 10−10 and the rate of LOH = 2.03 × 10−6/yr in Schwann cells. In addition to new parameter estimates, we extend the approach to estimate the risk of both spontaneous and radiation-induced malignant transformation.Discussion We conclude that radiotherapy is likely to have a negligible excess risk of malignancy for sporadic VS, with a possible exception of rapidly growing tumours.Subject terms: CNS cancer, Cancer in the nervous system |
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