BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas.
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.
Lima
Jorge
J
Institute of Molecular Pathology and Immunology, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
Trovisco
Vítor
V
Soares
Paula
P
Máximo
Valdemar
V
Magalhães
João
J
Salvatore
Giuliana
G
Santoro
Massimo
M
Bogdanova
Tatyana
T
Tronko
Mykola
M
Abrosimov
Alexander
A
Jeremiah
Steve
S
Thomas
Gerry
G
Williams
Dillwyn
D
Sobrinho-Simões
Manuel
M
D002291:Carcinoma, Papillary / Q000235:genetics*; D002648:Child; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011210:Power Plants; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D018788:Radioactive Hazard Release; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*; D014455:Ukraine
D015513:Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf