Tissue distribution and functional aspects of the NF2 tumour suppressor gene

Neoplastic disease in humans may occur sporadically, that is without a clear familial disposition, or less commonly as an inherited disease. Several distinct familial cancer syndromes are known and the underlying genetic cause has been identified of a number of these 46. The tumours in these syndromes are usually phenotypically identical to their sporadically occurring counterparts. Both syndromes with benign and with malignant tumours are known. In cancer syndromes tumours generally develop at a younger age than those seen in the non-familial setting and are often multiple 101. Most inherited cancer syndromes with an autosomal dominant inheritance pattern are caused by mutations in tumour suppressor genes. Far fewer inherited cancer syndromes are caused by mutations in (proto-)oncogenes, notably mUltiple endocrine neoplaSia type 2 and familial medullary thyroid cancer caused by mutations in the RET gene 99, 107, hereditary papillary renal cell carcinoma caused by mutations in the MET gene 124 and some cases of familial melanoma caused by mutations in the CDK4 gene 165. In addition to the classical tumour suppressor genes and proto-oncogenes, other genes involved in hereditary cancer are DNA repair genes.