Multicolor lineage tracing reveals clonal architecture and dynamics in colon cancer. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Lamprecht, Sebastian; Schmidt, Eva; Blaj, Cristina; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 9
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-00976-9
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract Colon cancers are composed of phenotypically heterogeneous tumor cell subpopulations with variable expression of putative stem cell and differentiation antigens. While in normal colonic mucosa, clonal repopulation occurs along differentiation gradients from crypt base toward crypt apex, the clonal architecture of colon cancer and the relevance of tumor cell subpopulations for clonal outgrowth are poorly understood. Using a multicolor lineage tracing approach in colon cancer xenografts that reflect primary colon cancer architecture, we here demonstrate that clonal outgrowth is mainly driven by tumor cells located at the leading tumor edge with clonal axis formation toward the tumor center. While our findings are compatible with lineage outgrowth in a cancer stem cell model, they suggest that in colorectal cancer tumor cell position may be more important for clonal outgrowth than tumor cell phenotype. The clonal architecture of colon cancer and the relevance of tumor cell subpopulations for clonal outgrowth are poorly understood. Here, the authors describe the clonal architecture and dynamics in human colon cancer by using a multicolor lineage tracing approach in colon cancer xenografts.