title: BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC.
abstract: Rearrangement of RET proto-oncogene is the major event in the etiopathogenesis of papillary thyroid carcinoma (PTC). We report a high prevalence of BRAF(V599E) mutation in sporadic PTC and in PTC-derived cell lines. The BRAF(V599E) mutation was detected in 23 of 50 PTC (46%) and in three of four PTC-derived cell lines. The prevalence of the BRAF(V599E) 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 BRAF(V599E) mutation. BRAF(V599E) 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. BRAF(V599E) mutation did not coexist with alterations in any of the RAS genes in any of the tumors. These results suggest that BRAF(V599E) mutation is frequent in the etiopathogenesis of PTC. The BRAF(V599E) mutation appears to be an alternative event to RET/PTC rearrangement rather than to RAS mutations, which are rare in PTC. BRAF(V599E) may represent an alternative pathway to oncogenic MAPK activation in PTCs without RET/PTC activation.
authors.affiliation: Institute of Molecular Pathology and Immunology of the University of Porto, (IPATIMUP), Rua Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: Vítor
authors.initials: V
authors.lastname: Trovisco
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Rocha
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: Patrícia
authors.initials: P
authors.lastname: Castro
authors.forename: Ana
authors.initials: A
authors.lastname: Preto
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.forename: Tiago
authors.initials: T
authors.lastname: Botelho
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D002291:Carcinoma, Papillary / Q000209:etiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins