The gene(s) responsible for two additional dominantly inherited disorders involving cancer of the medullary thyroid, MEN 2B (MEN2B), and dominantly inherited MTC without additional clinical features (MTC1), also map to this region.
This family demonstrates some of the phenotypic features of the multiple endocrine neoplasia type 2B syndrome without the characteristic neoplasms or the mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B.
Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals.
Sequence analysis of germ-line DNA from MEN 2B patients revealed the existence of the same point mutation in the RET protooncogene in 34 unrelated individuals.
Since germline mutations in the RET proto-oncogene (RET) predisposing to tumor development in Familial Medullary Thyroid Carcinoma (FMTC), Multiple endocrine neoplasia type 2A (MEN 2A), and Multiple endocrine neoplasia type 2B (MEN 2B) were reported, it has become possible to identify gene carriers with a very high degree of accuracy.
Approximately 80% of sporadic MTC's had at least one subpopulation with the RET codon 918 mutation, which is a mutation previously detected in sporadic MTC as a somatic mutation and in multiple endocrine neoplasia type 2B as a germline mutation.
These changes in autophosphorylation suggest that the MEN2B mutation may result in the more aggressive MEN2B phenotype by altering the receptor's signaling capabilities.
Multiple endocrine neoplasia type 2B (MEN 2B) is caused by the mutation of a conserved methionine to a threonine in the catalytic domain of the RET kinase.
The multiple endocrine neoplasia type 2B point mutation alters long-term regulation and enhances the transforming capacity of the epidermal growth factor receptor.
Germline mutations in the RET protooncogene are associated with multiple endocrine neoplasia (MEN) type 2A, familial medullary thyroid carcinoma (FMTC), and MEN type 2B.