BRAF mutation in papillary thyroid carcinoma

Abstract

BRAF mutation is the most common genetic alternation in thyroid cancer, particularly in papillary thyroid cancer (PTC). Excessive activation of BRAF/MAPK signaling pathway due to BRAF mutation plays a central role in the tumorigenesis and development of PTC. The association of BRAF mutation with poor clinicopathological characteristics of PTC further demonstrated the importance of the BRAF mutation alternation in PTC. Detection of BRAF mutation on FNA specimen before surgery is recommended as a useful diagnostic marker and prognostic indicator for PTC, and thus influences surgeon's decision on management of PTC. Recent studies have focused on inhibition of BRAF activation and several small molecules have been developed as targeting therapy.

Keywords: BRAF mutation; BRAF/MAPK signaling pathway; papillary thyroid carcinoma; targeting therapy.

Figure 1

The activation of the mitogen-activated protein kinase (MAPK) pathway in thyroid cancer by mutant BRAF. The most common genetic alternation in papillary thyroid cancer, BRAF mutation, stimulates constitutive signaling which bypasses the need for extracellular mitogenic signals. Subsequently phosphorylation of downstream MER1/2 and ERK1/2 results in transcriptional regulation of various genes which are involved in cell proliferation, differential, survival, tumorigenesis, and the process of EMT.