Hoeflich Klaus P, Jaiswal Bijay, Davis David P, Seshagiri Somasekar
Genentech Inc., Department of Molecular Biology, South San Francisco, CA, USA.
Methods Enzymol. 2008;439:25-38. doi: 10.1016/S0076-6879(07)00403-X.
Somatic mutations in BRAF have been reported in 50 to 70% of melanomas. The most common mutation is a valine to glutamic acid substitution at codon 600 (V600E). (V600E)BRAF constitutively activates ERK signaling and promotes proliferation, survival, and tumor growth. However, although BRAF is mutated in up to 80% of benign nevi, they rarely progress into melanoma. This implicates the BRAF mutation to be an initiating event that requires additional lesions in the genome for full-blown progression to melanoma. Even though the mutations appear early during the pathogenesis of melanoma, targeted BRAF knockdown using inducible shRNA in melanoma cell lines with BRAF mutations shows that BRAF is required for growth and maintenance of tumor in xenograft models.
据报道，50%至70%的黑色素瘤存在BRAF体细胞突变。最常见的突变是密码子600处缬氨酸被谷氨酸取代（V600E）。（V600E）BRAF持续激活ERK信号传导，促进增殖、存活和肿瘤生长。然而，尽管高达80%的良性痣存在BRAF突变，但它们很少进展为黑色素瘤。这表明BRAF突变是一个起始事件，需要基因组中的其他损伤才能完全进展为黑色素瘤。尽管这些突变在黑色素瘤发病机制的早期就出现了，但在具有BRAF突变的黑色素瘤细胞系中使用可诱导的短发夹RNA（shRNA）靶向敲低BRAF表明，在异种移植模型中，BRAF是肿瘤生长和维持所必需的。
