Mosaic Analysis with Double Markers (MADM) Reveals Tumor Cell-of-Origin in Glioma
By Chong Liu, J. Sage, Michael R. Miller, R. Verhaak, S. Hippenmeyer, H. Vogel, O. Foreman, R. Bronson, A. Nishiyama, Liqun Luo and 1 more. Cell, 2011
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SUMMARY 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 pre-malignant stages to identify the cancer cell-of-origin.
Subfields: Cancer Research, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/c02df1f113522d2e02803d1a7a76df9c13bde6c6
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Citations in the corpus
- Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma (2013, background): “…profiling of GBM has consistently shown the PN and MES subtypes, parallel efforts on GSCs have been limited, and mouse models representative of transcriptome subtypes of GBM are only beginning to emerge (Chow et al., 2011; Friedmann-Morvinski et al., 2012; Koso et al., 2012; Liu et al., 2011).”