High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.

摘要: Thyroid papillary cancers (PTCs) are associated with activating mutations of genes coding for RET or TRK tyrosine kinase receptors, as well RAS genes. Activating BRAF were reported recently in most melanomas and a small proportion colorectal tumors. Here we show that somatic mutation BRAF, V599E, is the common genetic change PTCs (28 78; 35.8%). BRAF(V599E) unique to PTCs, not found any other types differentiated follicular neoplasms arising from same cell type (0 46). Moreover, there was no overlap between PTC RET/PTC, mutations, which altogether present 66% cases. The lack concordance these highly unlikely be chance occurrence. Because signaling proteins function along pathway thyroid cells, this represents paradigm human tumorigenesis through three effectors lying tandem.