B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Eighty percent of all thyroid cancers are papillary thyroid carcinomas (PTCs). Presence of a BRAF p.Val600Glu (V600E) mutation is highly specific for papillary thyroid carcinoma and is only rarely associated with the follicular variant PTC and other well-differentiated thyroid neoplasms or nodular goiters. The K601E mutation results in an amino acid substitution at position 601 in BRAF, occurring within the highly conserved motif of the kinase domain. This is the second most common BRAF mutation found in thyroid nodules after V600E. Unlike BRAF V600E, K601E is strongly associated with follicular-patterned cancer, particularly with the encapsulated follicular variant of PTC, and may also be found in follicular thyroid carcinomas. Overall, BRAF K601E mutant tumors may show better clinical outcomes than BRAF V600E positive tumors.
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