Early treatment of hereditary medullary thyroid carcinoma after attribution of multiple endocrine neoplasia type 2 gene carrier status by screening for ret gene mutations.
BACKGROUND
Germline missense point mutations of the ret proto-oncogene have been shown as causative in multiple endocrine neoplasia type 2 (MEN 2A and 2B) and in familial medullary thyroid carcinoma (FMTC). Most of the mutations are found in exon 10, 11, or 16 of the gene and are easily recognized by restriction analysis.


METHODS
Using restriction analysis, we screened 58 subjects from nine kindreds.


RESULTS
Family members (n = 16) already known to be affected with the disease carried the germline mutation. Among the 42 subjects apparently unaffected, 37 were not gene carriers and 5 were gene carriers. Basal and pentagastrin-stimulated serum calcitonin levels were normal in two patients and abnormal in three. All patients were treated with total thyroidectomy and central node dissection. In all cases multiple foci of MTC were shown at histologic examination.


CONCLUSIONS
Our data indicate that genetic screening of MEN2 pedigrees allows the early identification of gene carriers. Because surgery of MTC in the preclinical phase has high probability of curing these patients, we suggest genetic screening soon after birth and total thyroidectomy in gene carriers as early as possible.
D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D029721:Drosophila Proteins; D006580:Genetic Carrier Screening; D006801:Humans; D008969:Molecular Sequence Data; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila