biostudies-literaturePaterson CUnited States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research ProgramsUnited States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)National Institute for Health Research (NIHR)1843-1857https://www.ebi.ac.uk/biostudies/studies/S-EPMC9643471biostudies-literatureUnknown127(10)<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>This results in new estimates for the base-pair mutation rate u = 4.48 × 10^-10 and the rBritish journal of cancerA mechanistic mathematical model of initiation and malignant transformation in sporadic vestibular schwannoma.PMC9643471IS-BRC-1215-20007W81XWH1910334Smith MJHoad XPaterson CEvans DGRBozic IfalseA mechanistic mathematical model of initiation and malignant transformation in sporadic vestibular schwannoma.<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>This results in new estimates for the base-pair mutation rate u = 4.48 × 10^-10 and the r2022-01-01T00:00:00Z2022 Nov2025-04-04T19:27:38.104Z2025-02-19T01:57:04.044ZS-EPMC96434713609717610.1038/s41416-022-01955-8