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BRAF T1796A Transversion Mutation in Various Thyroid Neoplasms

Division of Endocrinology and Metabolism, Departments of Medicine (M.X., P.W.L.) and Otolaryngology-Head and Neck Surgery (G.W., D.S.), the Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Hospital for Endocrine Surgery (A.L.), Kiev, 252000 Ukraine; Departments of Pathology (G.T.) and Surgery (R.U.), Yale University School of Medicine, New Haven, Connecticut 06520; Washington Hospital Center and Medstar Research Institute (V.V., M.D.R.), Washington, DC 20010; and Division of Endocrinology and Metabolism, The Ohio State University (M.D.R.), Columbus, Ohio 43235

Address all correspondence and requests for reprints to: Mingzhao Xing, M.D., Ph.D., Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: mxing1{at}jhmi.edu.

A high prevalence of activating mutation of the B type Raf kinase (BRAF) gene was recently reported in papillary thyroid cancer (PTC). However, the frequency of this mutation in several other types of thyroid neoplasms was not thoroughly investigated. In the present study, in addition to PTC, we evaluated various thyroid tumor types for the most common BRAF T1796A mutation by direct genomic DNA sequencing. We found a high and similar frequency (45%) of the BRAF T1796A mutation in two geographically distinct PTC patient populations: one composed of sporadic cases from North America, and the other from Kiev, Ukraine, that included individuals who were exposed to the Chernobyl nuclear accident. In contrast, we found BRAF mutation in only 20% of anaplastic thyroid cancers and no mutation in medullary thyroid cancers and benign thyroid hyperplasia. We also confirmed previous reports that the BRAF T1796A mutation did not occur in benign thyroid adenomas and follicular thyroid cancers. Specific analysis of the Ukraine patients with confirmed history of radiation exposure failed to show a higher incidence of BRAF mutation. Our results suggest that frequent occurrence of BRAF mutation is inherently associated with PTC, irrespective of geographic origin, and is apparently not a radiation-susceptible mutation. The lack or low prevalence of BRAF mutation in other thyroid neoplasms is consistent with the notion that other previously defined genetic alterations on the same signaling pathway are sufficient to cause tumorigenesis in most thyroid neoplasms.

This work was supported in part by National Institutes of Health Grants UO1 CA 98-028 and RO1 DE13561-01 (to D.S.) and by American Cancer Society Grant RSG CNE-103291 (to M.D.R.).

M.X. is the recipient of a Johns Hopkins Clinician Scientist Award.

Present address for V.V. and M.D.R.: Divisions of Endocrinology and Oncology, The Ohio State University College of Medicine, 455D McCampbell Hall, 1581 Dodd Drive, Columbus, Ohio 43210.

Present address for G.T.: Anatomia Patologica, Ospedale Bellaria, Via Altura 3, 40139 Bologna, Italy.

Abbreviations: ATC, Anaplastic thyroid cancer; FTC, follicular thyroid cancer; MTC, medullary thyroid cancer; PTC, papillary thyroid cancer.

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