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Models for the development of tumours in neurofibromatosis 2 Woods, Ryan R.

Abstract

Neurofibromatosis 2 (NF2) is a rare genetic disease that affects approximately 1 in 40000 people, some of the characteristic features of this disease include the onset of multiple tumours on the cranial and spinal nerves, juvenile cataracts and hearing loss. Almost all affected individuals develop bilateral tumours of the Schwann cells that line the vestibular nerves; these tumours are called as vestibular schwannomas (VS). Evidence from molecular genetic studies has suggested that a "2-hit" hypothesis is appropriate for the development of VS in patients with NF2; that is to say that a tumour cell develops from a normal Schwann cell after the cell sustains two mutations to its genetic material. Several authors have proposed probabilistic models for this process and have shown that such models are consistent with incidence data for several different types of cancer. We will discuss a selection of probabilistic models for a "2-hit" hypothesis and present the results from the fitting of such models to incidence data from NF2 patients. Molecular evidence does not exclude the possibility that additional hits are necessary for the development of VS; we will discuss a "3-hit" model and compare the model's fit to both the data and to the fit of the "2-hit" models. Genotypephenotype correlations have been reported in patients with NF2 and thus a model that incorporates a patient's genotype is presented and discussed. Finally, a bivariate model is proposed to estimate the distributions of the ages at onset of both the first and second VS.

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