Original communicationMutation analysis of the RET proto-oncogene and early thyroidectomy: results of a Portuguese cancer centre
Section snippets
Subjects and methods
DNA was obtained from the peripheral blood of 158 individuals who were divided into 4 groups. Group A (n = 77) included patients with apparently sporadic MTC. Group B (n = 8) included patients presenting MTC associated with pheochromocytoma despite a negative family history for multiple endocrine neoplasia type 2 (MEN 2) (7 individuals) or presenting clinical features of MEN 2B (1 individual). Group C (n = 8) included patients with MTC and known to belong to clinically established FMTC/MEN 2
Results
Germline mutations in the RET proto-oncogene were identified in 3 of 77 (3.9%) apparently sporadic MTC patients, thus indicating heritable disease. Mutations were TGC620CGC; TTG790TTT, and GTG804ATG. It was not possible to define whether they corresponded to de novo or occult mutations.
All individuals in group B (n = 8) had a germline mutation in the RET proto-oncogene. Four different mutations were identified: TGC611TAC (1 case), TGC634CGC (5 cases), GTG804ATG (1 case), and ATG918ACG (1 case).
Discussion
In 98% of MEN 2A patients and in 90% of FMTC patients20 the germline RET mutation occurs in 1 of 5 cysteine codons of the extracellular domain of the RET protein: 609, 611, 618, 620 (exon 10), or 634 (exon 11). In the remaining cases, the mutation may occur in codon 630,21 another cysteine codon in exon 11, or in noncysteine-related codons located in the intracellular domain of the RET protein such as mutations affecting codons 768, 790, and 791 (exon 13); codon 804 (exon 14); or codon 891 in
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