Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032 | Rubinstein et al. Journal of Translational Medicine 2010 8 67 http content 8 1 67 JOURNAL OF TRANSLATIONAL MEDICINE COMMENTARY Open Access Incidence of the V600K mutation among melanoma patients with BRAF mutations and potential therapeutic response to the specific BrAF inhibitor PLX4032 líll Di I Hi n ci oi n 1 l l rim Q7nnl2 Anno c D2 li lz3 Ari 3n4 Dl ino rhan i5 Ạ ntnncil H Rci rr H i D Hi5 Jill C Rubinstein IVIdllU sznol Annd C Pdvlick Stepildn Allydll Eldine Cheng Antonelld Bdccnioccili Harriet M Kluger2 Deepdk Ndrdydn4 Ruth Hdldbdn5 Abstract Activdting mutdtions in BRAF kindse dre common in meldnomds. Clinicdl tridls with PLX4032 the mutdnt-BRAF inhibitor show promising prelimindry results in pdtients selected for the presence of V600E mutdtion. However dctivdt-ing V600K mutdtion is the other most common mutdtion yet pdtients with this vdridnt dre currently excluded from the PLX4032 tridls. Here we present evidence thdt d pdtient bedring the BRAF V600K mutdtion responded remdrk-dbly to PLX4032 suggesting thdt clinicdl tridls should include dll pdtients with dctivdting BRAF V600E K mutdtions. Commentary BRAF is a serine threonine protein kinase encoded on chromosome 7q34 that activates the MAP kinase ERK-signaling pathway see KEGG Pathways Database . Approximately 42 of melanomas harbor activating BRAF mutations see COSMIC Database Wellcome Sanger Trust . Most commonly the valine at amino acid 600 is replaced by glutamate V600E through mutation of a single nucleotide GTG to GAG . Another known mutation at this site involves two nucleotides GTG to AAG substituting lysine for valine V600K see Table 1 for statistics on the frequency of these mutations reported in melanoma . The specific BRAF inhibitor PLX4032 Plexxikon Inc. Berkeley CA suppresses the activated oncogenic pathway by inhibiting the ERK kinase cascade. High objective response rates were observed in the phase I clinical trial of PLX4032 in the cohort of melanoma .
