One patient having a mutation in exon 16 (Met918Thr) presented with the MEN2B phenotype, six patients from two families had hereditary MTC without pheochromocytoma (pheo) and primary hyperparathyroidism (PHPT), whereas 33 patients from 15 families showed the MEN2A phenotype.
Mutation analysis of exon 16 of the RET proto-oncogene revealed germline M918T and thus, a molecular diagnosis of multiple endocrine neoplasia type 2B (MEN 2B).
Forty-four MEN 2B patients carrying inherited (3 patients) and de novo (41 patients) M918T RET mutations were examined for signs and symptoms prompting MEN 2B.
Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B</span> (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype.
In multiple endocrine neoplasia 2B (MEN-2B) patients expressing RET(M918T), nuclear enrichment of STAT3 and elevated expression of CXCR4 was detected in metastatic thyroid C-cell carcinoma in the liver.
Although there were no syndromic features or a positive family history, mutation analysis of the RET proto-oncogene showed a de novo germline Met918Thr mutation in both patients, confirming the diagnosis of multiple endocrine neoplasia type 2B (MEN 2B).
Thus, while our results support the conclusion that the Met918Thr substitution is responsible for MEN2B, they suggest that the substrate specificity of the RET kinase does not interfere with its normal role in the development of the kidneys and enteric nervous system.
They are represented by the Met918Thr substitution (exon 16) typical of Multiple Endocrine Neoplasia type 2B (MEN2B) and, to a lesser extent, by nucleotide changes occurring at one of five critical cysteine residues (exons 10 and 11) typical of MEN type 2A (MEN2A).
More than 90% of M918T carriers with multiple endocrine neoplasia type 2B (MEN 2B) harbor de novo mutations in the REarranged during Transfection (RET) protooncogene.
Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features.
We also examined the sensitivity of RET (M918T), a RET mutation prevalent in aggressive multiple endocrine neoplasia type 2B, to these TKIs in the context of BaF3/KR cells.
This family of 11 individuals with familial MTC type of MEN 2A syndrome demonstrated the moderate risk RET p.Val804Met (protein valine at residue 804 replaced by methionine) genetic mutation, with 2 of the relatives presenting with dermal hyperneury, cutaneous lesions classically described in MEN 2B syndrome, and 1 relative also showing multiple sclerotic fibromas, a cutaneous manifestation of PTEN (phosphatase and tensin homologue) hamartoma-tumor syndrome.