Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
Liu C,Sage JC,Miller MR,Verhaak RG,Hippenmeyer S,Vogel H,Foreman O,Bronson RT,Nishiyama A,Luo L,Zong Hdoi
10.1016/j.cell.2011.06.014subject
Has Abstractpub_date
2011-07-22 00:00:00pages
209-21issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(11)00656-8journal_volume
146pub_type
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