GENETICS OF FAMILIAL AND NONFAMILIAL SKULL BASE TUMORS

Many tumours of the skull base, including schwannomas, paragangliomas, meningiomas and anterior pituitary tumours occur both as sporadic tumours and in clear cut familial syndromes. These cancers' highly penetrant dominantly inherited syndromes have proven to be a rich resource for locating tumour genes, most of which are of the tumour suppressor type. Recently, the gene for type 2 neurofibromatosis (NF2) was isolated by the technique of positional cloning. The NF2 gene has now been demonstrated to be involved in the pathogenesis of both familial and non-familial vestibular schwannomas as well as meningiomas. The presence of inactivating mutations within this gene suggests that it acts as a tumour suppressor and the mechanism has been shown to comply with a 'two hit' mutation model. Hereditary tumours constitute a small proportion of all cases, but evidence from studies of tumours such as vestibular schwannoma and meningioma have shown that their genes are also relevant to the much more common non-familial forms of the same tumour. This paper briefly describes the approach to locating tumour genes, and reviews our current knowledge regarding the chromosomal location and function of genes responsible for familial tumours involving the skull base. The genetic mechanisms of tumourigenesis are discussed as are the prospects for the development of novel forms of diagnosis and treatment.