Gene copy number variation profiling by microarray

Here, we investigate focal amplification patterns in and around the BRAF locus in BRAFV600Emutant COLO205 cells that acquire resistance to the MEK inhibitor Sleumetinib / AZD6244 / ARRY-142886. We find that BRAF amplifications occur frequently in COLO205 cells during acquisition of selumetinib resistance and that BRAFamplifications pre-exist selumetinib treatment but occurs predominantly via de novo mutations Genomic DNA extracted from parental COLO205 cells and their selumetinib-resistant dervatives were profiled for gene copy number variation using Infinium CytoSNP 850K beadchip microarrays (Illumina)

本研究针对携带BRAFV600E突变的COLO205细胞及其对MEK抑制剂司美替尼（Selumetinib / AZD6244 / ARRY-142886）产生耐药性的细胞系，探究BRAF基因座及其上下游区域的局灶扩增模式。研究发现，在COLO205细胞获得司美替尼耐药性的过程中，BRAF基因扩增频发；且BRAF扩增在司美替尼治疗前即已存在，其发生主要源于新发突变（de novo mutation）。本研究通过Illumina公司的Infinium CytoSNP 850K微球芯片微阵列，对亲本COLO205细胞及其司美替尼耐药衍生细胞的基因组DNA开展基因拷贝数变异检测分析。