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 tum ours and in clear cut familial syndromes. These cancers' highly penetr ant dominantly inherited syndromes have proven to be a rich resource f or locating tumour genes, most of which are of the tumour suppressor t ype. Recently, the gene for type 2 neurofibromatosis (NF2) was isolate d by the technique of positional cloning. The NF2 gene has now been de monstrated 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 't wo hit' mutation model. Hereditary tumours constitute a small proporti on of all cases, but evidence from studies of tumours such as vestibul ar schwannoma and meningioma have shown that their genes are also rele vant to the much more common non-familial forms of the same tumour. Th is paper briefly describes the approach to locating tumour genes, and reviews our current knowledge regarding the chromosomal location and f unction of genes responsible for familial tumours involving the skull base. The genetic mechanisms of tumourigenesis are discussed as are th e prospects for the development of novel forms of diagnosis and treatm ent.