CDX2 is an amplified lineage-survival oncogene in colorectal cancer

摘要: The mutational activation of oncogenes drives cancer development and progression. Classic oncogenes, such as MYC RAS, are active across many different types. In contrast, “lineage-survival” represent a distinct emerging class typically comprising transcriptional regulators specific cell lineage that, when deregulated, support the proliferation survival cancers derived from that lineage. Here, in large collection colorectal lines tumors, we identify recurrent amplification chromosome 13, an alteration highly restricted to colorectal-derived cancers. A minimal region on 13q12.2 pinpoints caudal type homeobox transcription factor 2 (CDX2), regulator normal intestinal differentiation, target amplification. contrast its described role tumor suppressor, CDX2 amplified is required for cells. Further, profiling, binding-site analysis, functional studies link Wnt/β-catenin signaling, itself key oncogenic pathway cancer. These data characterize lineage-survival oncogene deregulated Our findings challenge prevailing view suppressor uncover additional piece multistep model tumorigenesis.