Abstract
Rearrangement of RET proto-oncogene is the major event in the etiopathogenesis of papillary thyroid carcinoma (PTC). We report a high prevalence of BRAFV599E mutation in sporadic PTC and in PTC-derived cell lines. The BRAFV599E mutation was detected in 23 of 50 PTC (46%) and in three of four PTC-derived cell lines. The prevalence of the BRAFV599E mutation in PTC is the highest reported to date in human carcinomas, being only exceeded by melanoma. PTC with RET/PTC rearrangement as well as the TPC-1 cell line (the only one harboring RET/PTC rearrangement) did not show the BRAFV599E mutation. BRAFV599E mutation was not detected in any of 23 nodular goiters, 51 follicular adenomas and 18 follicular carcinomas. A distinct mutation in BRAF (codon K600E) was detected in a follicular adenoma. Activating mutations in RAS genes were detected in 15% of FA, 33% of FTC and 7% of PTC. BRAFV599E mutation did not coexist with alterations in any of the RAS genes in any of the tumors. These results suggest that BRAFV599E mutation is frequent in the etiopathogenesis of PTC. The BRAFV599E mutation appears to be an alternative event to RET/PTC rearrangement rather than to RAS mutations, which are rare in PTC. BRAFV599E may represent an alternative pathway to oncogenic MAPK activation in PTCs without RET/PTC activation.
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Acknowledgements
We thank the contribution that Carla Oliveira gave to this work. We are grateful to the ‘Fundação para a Ciência e Tecnologia’ for grant support to Vítor Trovisco, Ana Rocha, Jorge Lima, Patrícia Castro, Ana Preto and Tiago Botelho. This work was supported by Fundação para a Ciência e Tecnologia (FCT), project POCTI/CBO/38567/2001.
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Soares, P., Trovisco, V., Rocha, A. et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 22, 4578–4580 (2003). https://doi.org/10.1038/sj.onc.1206706
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DOI: https://doi.org/10.1038/sj.onc.1206706
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