Functional Characterization of the Tl 799-1801 del and Al 799-1816ins BRAF Mutations in Papillary Thyroid Cancer

摘要

The RAS -> RAF -> MEK -> MAP kinase/ERK signaling pathway (MAP kinase pathway) is a conserved protein kinase cascade that regulates cell growth, proliferation, and differentiation in response to growth factors, cytokines, and hormones.1 Constitutive activation of this pathway is common in human cancers. Activating mutations in the gene for the B-type RAF or BRAF were identified in many human cancers.2 Over 40 missense mutations have been identified in the BRAF gene, the majority of which clusters in exons 11 and 15 and affects residues located within the kinase domain of the protein.3 The T1799A point BRAF mutation in exon 15, resulting in a V600E substitution (i.e., valine replaced by glutamic acid) in BRAF protein accounts for about 90% of all the oncogenic BRAF mutations.3 Numerous studies have shown frequent occurrence of this mutation in papillary thyroid cancer (PTC), with a prevalence of 44% on average.