RET MUTATIONS IN HUMAN-DISEASE

The RET proto-oncogene is at the origin of the one of the most interes ting models of human disease caused by mutations in a receptor tyrosin e kinase gene. Somatic rearrangements of RET are involved in the aetio logy of a variable proportion of papillary thyroid carcinomas (PTC), t he most common type of thyroid tumour whose prevalence is increasing i n areas heavily exposed to radioactive fallout after the Chernobyl acc ident of 1986. Moreover, germline RET mutations are associated with th e three variants of the inherited cancer syndrome known as multiple en docrine neoplasia type 2 (MEN2A, MEN2B and FMTC). Finally, RET mutatio ns or heterozygous deletions of the whole gene cause the autosomal dom inant form of Hirschsprung disease (HSCR), a congenital disorder of th e enteric nervous system (ENS).