Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours

Abstract

The susceptibilIty locl for the three multiple endocrine neoplasIa (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosIne kinase. The majority of MEN 2A and familIal medullary thyrold carcInoma results from mlssense mutations within one of five cysteIne codons In the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonlne for a methlonine at codon 918 in the tyrosIne kInase catalytIc domain, In the germllne of 26 of 28 apparently distinct families with MEN 2B. DNA from five of 13 apparently sporadIc MTC and one of 12 apparently sporadic phaeochromocytomas harboured a sImIlar mutation, but the corresponding germllne DNA was wildtype In each case.