Molecular evaluation of BRAF gene mutation in thyroid tumors: Significant association with papillary tumors and extra thyroidal extension indicating its role as a biomarker of aggressive disease.

BACKGROUND: Somatic mutation of the BRAF gene is one to be the most commonly known genetic change in thyroid tumors especially papillary thyroid cancers. The T1799A activating point mutation is detected in >98% of the thyroid tumors, and result in substitution of amino acid valine at position 600 to glutamic acid. METHOD: In this study, we evaluated BRAF mutation in 95 Indian thyroid tumors by pyrosequencing assay. RESULTS: Overall, 36 cases (38%) showed presence of BRAF V600E mutation, while none of the cases showed V600 K mutation. BRAF mutation was found predominantly in female patients in comparison to males (38.4% vs. 36.4%, p = .86). Likewise, smaller sized tumors (≤2.0 cm) showed increased frequency of BRAF mutation as compared to larger sized tumors which were greater than equal to 2 cm (46% vs. 34.4%, p = .64). Furthermore, the frequency of BRAF mutations was significantly higher in conventional PTC tumor type in comparison to non-conventional and other than PTC tumor type (56% vs. 35% vs. 4%, p = .0007). Notably, a significant correlation between presence of BRAF mutation and extra-thyroidal extension was noted. Nevertheless, presence of BRAF mutation was neither associated with capsular/vascular invasion, nor with tumor necrosis. CONCLUSIONS: Pyrosequencing assay was found to be highly sensitive and accurate method for detecting BRAF point mutations. The frequency and distribution pattern of BRAF mutations is similar to global reports. Furthermore, association of BRAF mutation with extra thyroidal extension indicates its aggressive nature and thus can provide insights into the progression of thyroid tumors from less aggressive to poorly differentiated subtype.