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Institute of Molecular Pathology and Immunology (J.L., V.T., P.S., V.M., J.M., A.A., M.S.-S.) and Medical Faculty (J.L., V.T., P.S., M.S.-S.), University of Porto, 4200-465 Porto, Portugal; Department of Pathology (J.M., M.S.-S.), Hospital S. João, 4200 Porto, Portugal; Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare (G.S., M.S.), Università di Napoli Federico II, 80137 Italia; Institute of Endocrinology and Metabolism (T.B., M.T.), 254114 Kiev, Ukraine; Medical Radiological Research Centre of Russian Academy of Medical Sciences (A.A.), 249020 Obninsk, Russian Federation; South West Wales Cancer Institute (S.J., G.T.), Swansea Clinical School, Singleton Hospital, SA2 8QA Swansea, United Kingdom; and Strangeways Research Laboratory (D.W.), University of Cambridge, CB1 8RN Cambridge, United Kingdom
Address all correspondence and requests for reprints to: Dr. Manuel Sobrinho-Simões, Institute of Molecular Pathology and Immunology, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal. E-mail: ssimoes{at}ipatimup.pt.
The BRAF gene has been shown to be a major target for mutations in papillary thyroid carcinoma (PTC) (36–69%), which forms almost all of the over 2000 cases of thyroid carcinoma that have occurred in Chernobyl. BRAF is activated by point mutation, and were it to occur at a high frequency in Chernobyl-related tumors, it would challenge the dominant role of double-strand breaks in radiation-induced PTC. In a previous study, we detected the BRAF V600E mutation in 46% (23 of 50) of sporadic adult PTC. Using the same methodology, we have analyzed 34 post-Chernobyl PTC and detected RET/PTC rearrangements in 14 (41%) and BRAF mutations (V600E) in four (12%). These two alterations did not coexist in any PTCs. The mean age at exposure of patients with PTC showing BRAF mutation was higher than that of patients with tumors without BRAF mutation irrespective of their RET status. We have also analyzed 17 sporadic cases of childhood PTC and found that only one (6%) harbored the BRAF V600E mutation. We conclude that the frequency of BRAF mutations is significantly lower (P = 0.0008) in post-Chernobyl PTC than in adult sporadic PTC, whereas no significant difference was found between post-Chernobyl and sporadic childhood PTCs.
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