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Low Frequency of BRAF^T1796A Mutations in Childhood Thyroid Carcinomas

Department of Molecular Medicine (A.K., H.N., K.A., S.Y.), International Health and Radiation Research (V.A.S., S.Y.), Department of Radiation Epidemiology (Y.S.), Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, and Department of Surgery (A.K., T.N.), Takashi Nagai Memorial International Hibakusha Medical Center (A.O., S.Y.), Nagasaki University Hospital, Nagasaki 852-8523, Japan; Department of Pathology, National Nagasaki Medical Center (M.I.), Omura 856-8562, Japan; Ito Hospital (N.I., K.S., K.I.), Tokyo 150-8308, Japan; South West Wales Cancer Institute, Singleton Hospital (S.J., G.A.T.), Swansea, United Kingdom SA2 8QA; and Laboratory of Morphology of Endocrine System, Institute of Endocrinology and Metabolism, Academy of Medical Sciences of Ukraine (T.I.B., M.D.T.), Kiev 04114, Ukraine

Address all correspondence and requests for reprints to: Dr. Hiroyuki Namba, Department of Molecular Medicine, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. E-mail: namba{at}net.nagasaki-u.ac.jp.

A high prevalence of the activating BRAF mutation, BRAF^T1796A, is observed in adult papillary thyroid carcinomas (PTCs). The prognosis of childhood PTCs is generally fairly good despite the fact that distant metastases are often documented in these cases. To investigate the differences between the characteristics of childhood and adult PTCs, we analyzed both BRAF^T1796A and RAS mutations in 31 Japanese and 48 post-Chernobyl Ukrainian thyroid carcinomas. In the 31 Japanese childhood cases, BRAF^T1796A was found in only one instance (3.2%), and no RAS mutations were detected. In the Ukrainian subjects, of the 15 childhood and the 33 adolescent and young adult PTCs examined, the BRAF^T1796A mutation was found in zero and eight cases, respectively, and RAS mutations were found in two of the young adult cases. In addition, 17 of the 48 Ukrainian cases showed expression of the RET tyrosine kinase region, indicating the existence of RET/PTC rearrangements. Unlike adult PTCs, we could detect no positive association between BRAF^T1796A mutations and clinical parameters in the childhood carcinomas, suggesting that a low prevalence of BRAF^T1796A is a common feature of PTCs in children regardless of radiation exposure levels. The differences in the prevalence of BRAF^T1796A mutations between childhood and adult cases of PTC may well reflect inherent differences in the clinical features of these cancers between the two age groups.

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