This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lima, J. Articles by Sobrinho-Simões, M. Search for Related Content PubMed PubMed Citation Articles by Lima, J. Articles by Sobrinho-Simões, M. Pubmed/NCBI databases Medline Plus Health Information Thyroid Cancer

BRAF Mutations Are Not a Major Event in Post-Chernobyl Childhood Thyroid Carcinomas

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.

This article has been cited by other articles:

				J P. Couto, H Prazeres, P Castro, J Lima, V Maximo, P Soares, and M Sobrinho-Simoes How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer J. Clin. Pathol., May 1, 2009; 62(5): 414 - 421. [Abstract] [Full Text] [PDF]

				A. Burniat, L. Jin, V. Detours, N. Driessens, J.-C. Goffard, M. Santoro, J. Rothstein, J. E. Dumont, F. Miot, and B. Corvilain Gene Expression in RET/PTC3 and E7 Transgenic Mouse Thyroids: RET/PTC3 But Not E7 Tumors Are Partial and Transient Models of Human Papillary Thyroid Cancers Endocrinology, October 1, 2008; 149(10): 5107 - 5117. [Abstract] [Full Text] [PDF]

				K. Hamatani, H. Eguchi, R. Ito, M. Mukai, K. Takahashi, M. Taga, K. Imai, J. Cologne, M. Soda, K. Arihiro, et al. RET/PTC Rearrangements Preferentially Occurred in Papillary Thyroid Cancer among Atomic Bomb Survivors Exposed to High Radiation Dose Cancer Res., September 1, 2008; 68(17): 7176 - 7182. [Abstract] [Full Text] [PDF]

				J. Abubaker, Z. Jehan, P. Bavi, M. Sultana, S. Al-Harbi, M. Ibrahim, A. Al-Nuaim, M. Ahmed, T. Amin, M. Al-Fehaily, et al. Clinicopathological Analysis of Papillary Thyroid Cancer with PIK3CA Alterations in a Middle Eastern Population J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 611 - 618. [Abstract] [Full Text] [PDF]

				A Salajegheh, E B Petcu, R A Smith, and A K-Y Lam Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists Postgrad. Med. J., February 1, 2008; 84(988): 78 - 82. [Abstract] [Full Text] [PDF]

				G. Riesco-Eizaguirre and P. Santisteban New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy Endocr. Relat. Cancer, December 1, 2007; 14(4): 957 - 977. [Abstract] [Full Text] [PDF]

				R. Ciampi and Y. E. Nikiforov RET/PTC Rearrangements and BRAF Mutations in Thyroid Tumorigenesis Endocrinology, March 1, 2007; 148(3): 936 - 941. [Abstract] [Full Text] [PDF]

				M. Santoro, R. M. Melillo, and A. Fusco RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture. Eur. J. Endocrinol., November 1, 2006; 155(5): 645 - 653. [Abstract] [Full Text] [PDF]

				M Niedziela Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr. Relat. Cancer, June 1, 2006; 13(2): 427 - 453. [Abstract] [Full Text] [PDF]

				L Fugazzola, E Puxeddu, N Avenia, C Romei, V Cirello, A Cavaliere, P Faviana, D Mannavola, S Moretti, S Rossi, et al. Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr. Relat. Cancer, June 1, 2006; 13(2): 455 - 464. [Abstract] [Full Text] [PDF]

				P. Castro, A. P. Rebocho, R. J. Soares, J. Magalhaes, L. Roque, V. Trovisco, I. Vieira de Castro, M. Cardoso-de-Oliveira, E. Fonseca, P. Soares, et al. PAX8-PPAR{gamma} Rearrangement Is Frequently Detected in the Follicular Variant of Papillary Thyroid Carcinoma J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 213 - 220. [Abstract] [Full Text] [PDF]

				M. Hatch, E. Ron, A. Bouville, L. Zablotska, and G. Howe The Chernobyl Disaster: Cancer following the Accident at the Chernobyl Nuclear Power Plant Epidemiol. Rev., July 1, 2005; 27(1): 56 - 66. [Full Text] [PDF]

				P. Castro, L. Roque, J. Magalhaes, and M. Sobrinho-Simoes A Subset of the Follicular Variant of Papillary Thyroid Carcinoma Harbors the PAX8-PPAR{gamma} Translocation International Journal of Surgical Pathology, July 1, 2005; 13(3): 235 - 238. [Abstract] [PDF]

				M Xing BRAF mutation in thyroid cancer Endocr. Relat. Cancer, June 1, 2005; 12(2): 245 - 262. [Abstract] [Full Text] [PDF]

				J. A. Fagin Challenging Dogma in Thyroid Cancer Molecular Genetics--Role of RET/PTC and BRAF in Tumor Initiation J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4264 - 4266. [Full Text] [PDF]