MOLECULAR-BIOLOGY OF THE MEN2 GENE

Cancer is a genetic disease caused by 'gain of function' mutations of oncogenes and 'loss of function' mutations of tumour suppressors and o f genes involved in DNA repair mechanisms, The RET gene encodes a tyro sine kinase receptor for molecules belonging to the glial cell line-de rived neurotrophic factor (GDNF) family. RET is a paradigmatic example of how different mutations of a single gene can lead to different neo plastic phenotypes, Indeed, gene rearrangements, often caused by chrom osomal inversions, activate the oncogenic potential of RET in a fracti on of human thyroid papillary carcinomas. On the other hand, different point mutations activate RET in familial multiple endocrine neoplasia syndromes familial medullary thyroid carcinoma (FMTC), MEN-2A and MEN -2B. Little information is so far available on the biochemical mechani sms by which the potent transforming and mitogenic signals of RET are delivered to the nucleus. However, recent data indicate coupling to th e Shc-Ras-MAPK pathway as a necessary step in RET signal transduction.