Matt van de Rijn

Publication Details

  • CDX2 is an amplified lineage-survival oncogene in colorectal cancer PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Salari, K., Spulak, M. E., Cuff, J., Forster, A. D., Giacomini, C. P., Huang, S., Ko, M. E., Lin, A. Y., van de Rijn, M., Pollack, J. R. 2012; 109 (46): E3196-E3205


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

    View details for DOI 10.1073/pnas.1206004109

    View details for Web of Science ID 000311576300010

    View details for PubMedID 23112155

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