title: A newly identified missense mutation in RET codon 666 is associated with the development of medullary thyroid carcinoma.
abstract: A 38-year-old woman with a thyroid nodule measuring approximately 2 cm was suspected to have medullary thyroid carcinoma (MTC) because of markedly elevated serum calcitonin and carcinoembryonic antigen levels. There were no signs of pheochromocytoma, whereas primary hyperparathyroidism was suspected based on the findings of inappropriate hypersecretion of parathyroid hormone although no parathyroid tumor was detected with imaging studies. RET mutation analysis revealed a novel germline missense mutation in codon 666, c.1997A>G (p.K666R). She underwent total thyroidectomy with lymphadenectomy and simultaneous total parathyroidectomy with autotransplantation of parathyroid tissue. She was given calcium lactate and alfacalcidol to prevent postoperative hypocalcemia. Pathological findings of the thyroid tumor were compatible with MTC, but the resected parathyroid glands were intact. To our knowledge, c.1997A>G (p.K666R) is a new RET mutation. This is a minor variant, but it is significant because of the possible pathogenicity in tumor formation. It is often difficult to determine whether MTC is generated as part of MEN2-related disease or familial MTC when it is a unique manifestation. In addition, it is still unclear whether all missense mutations in this codon reported previously will lead to the same clinical course and prognosis. Further careful observations of clinical presentation are required to determine the clinical features associated with this variant.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Toru
authors.initials: T
authors.lastname: Hanamura
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ito
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchino
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakurai
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Komatsu
mesh_terms: D000328:Adult; D018276:Carcinoma, Medullary / Q000151:congenital* / Q000235:genetics; D003062:Codon; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D020125:Mutation, Missense; D010282:Parathyroid Neoplasms / Q000601:surgery; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D016606:Thyroid Nodule / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D003062:Codon; D051096:Proto-Oncogene Proteins c-ret