Liu, Chong; Sage, Jonathan C; Miller, Michael R; Verhaak, Roel G; Hippenmeyer, SimonISTA ; Vogel, Hannes; Foreman, Oded; Bronson, Roderick T; Nishiyama, Akiko; Luo, Liqun; Zong, Hui
Cancer cell of origin is difficult to identify by analyzing cells within terminal stage tumors, whose identity could be concealed by the acquired plasticity. Thus, an ideal approach to identify the cell of origin is to analyze proliferative abnormalities in distinct lineages prior to malignancy. Here, we use mosaic analysis with double markers (MADM) in mice to model gliomagenesis by initiating concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs). Surprisingly, MADM-based lineage tracing revealed significant aberrant growth prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in any other NSC-derived lineages or NSCs themselves. Upon tumor formation, phenotypic and transcriptome analyses of tumor cells revealed salient OPC features. Finally, introducing the same p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis. Our findings suggest OPCs as the cell of origin in this model, even when initial mutations occur in NSCs, and highlight the importance of analyzing premalignant stages to identify the cancer cell of origin.
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Liu C, Sage J, Miller M, et al. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 2011;146(2):209-221. doi:10.1016/j.cell.2011.06.014
Liu, C., Sage, J., Miller, M., Verhaak, R., Hippenmeyer, S., Vogel, H., … Zong, H. (2011). Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. Cell Press. https://doi.org/10.1016/j.cell.2011.06.014
Liu, Chong, Jonathan Sage, Michael Miller, Roel Verhaak, Simon Hippenmeyer, Hannes Vogel, Oded Foreman, et al. “Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in Glioma.” Cell. Cell Press, 2011. https://doi.org/10.1016/j.cell.2011.06.014.
C. Liu et al., “Mosaic analysis with double markers reveals tumor cell of origin in glioma,” Cell, vol. 146, no. 2. Cell Press, pp. 209–221, 2011.
Liu C, Sage J, Miller M, Verhaak R, Hippenmeyer S, Vogel H, Foreman O, Bronson R, Nishiyama A, Luo L, Zong H. 2011. Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell. 146(2), 209–221.
Liu, Chong, et al. “Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in Glioma.” Cell, vol. 146, no. 2, Cell Press, 2011, pp. 209–21, doi:10.1016/j.cell.2011.06.014.