Comprehensive Genomic Alterations in Common Cancer Cell Lines Revealed by Exome Sequencing

摘要: It is well established that genomic alterations play an essential role in oncogenesis, disease progression, and response of tumors to therapeutic intervention. The advances next-generation sequencing technologies (NGS) provide unprecedented capabilities scan genomes for changes such as mutations, deletions, chromosomal copy number. However, the cost full-genome still prevents routine application NGS many areas. Capturing coding exons genes (the “exome”) can be a cost-effective approach identifying result alteration protein sequences. We applied exome technology (Roche NimbleGen capture paired with 454 sequencing) identify sequence variation mutations eight commonly used cancer cell lines from variety tissue origins (A2780, A549, Colo205, GTL16, NCI-H661, MDA-MB468, PC3, RD). showed this accurately variation, providing ~95 % concordance Affymetrix SNP Array 6.0 performed on same lines. Furthermore, we detected 19 21 reported Sanger COSMIC database these identified average 2,779 potential novel variations/mutations per line, which 1,904 were non-synonymous. Many non-synonymous kinases known cancer-related genes. In addition confirmed read depth data estimate high-level gene amplifications homologous deletions. summary, demonstrate reliable way genomes, have generated comprehensive catalogue regions These findings could important insights into pathways mechanisms resistance anticancer therapies.