Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma

SummaryTo assess the mutational status of BRAF in FVPTC, we directly sequenced the genomic DNA of 30 primary FVPTC samples. BRAF mutations were found in only 4 (13%) tumors. We also identified a previously unknown (novel) mutation in the activation kinase domain of the BRAF (A598V), replacing alanine with valine. Functional analysis showed that this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors. The effect of this mutation on the structural formation of the protein is highlighted. Our results confirm the infrequency of BRAF (V600E) mutation in FVPTC and identify a novel (A598V) mutation of this gene.