BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas

被引:137
作者
Lima, J
Trovisco, V
Soares, P
Máximo, V
Magalhaes, J
Salvatore, G
Santoro, M
Bogdanova, T
Tronko, M
Abrosimov, A
Jeremiah, S
Thomas, G
Williams, D
Sobrinho-Simoes, M
机构
[1] Univ Porto, Inst Mol Pathol & Immunol, P-4200465 Oporto, Portugal
[2] Univ Porto, Fac Med, P-4200465 Oporto, Portugal
[3] Hosp Sao Joao, Dept Pathol, P-4200 Oporto, Portugal
[4] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Consiglio Nazl Ric, Ctr Endocrinol & Oncol Sperimentale, I-80137 Naples, Italy
[5] Inst Endocrinol & Metab, UA-254114 Kiev, Ukraine
[6] Russian Acad Med Sci, Med Radiol Res Ctr, Obninsk 249020, Russia
[7] Singleton Hosp, Swansea Clin Sch, S W Wales Canc Inst, Swansea SA2 8QA, W Glam, Wales
[8] Univ Cambridge, Strangeways Res Lab, Cambridge CB1 8RN, England
关键词
D O I
10.1210/jc.2003-032224
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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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页码:4267 / 4271
页数:5
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