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Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution

Author(s)
Yang, Dian; Jones, Matthew G; Naranjo, Santiago; Rideout, William M; Min, Kyung Hoi Joseph; Ho, Raymond; Wu, Wei; Replogle, Joseph M; Page, Jennifer L; Quinn, Jeffrey J; Horns, Felix; Qiu, Xiaojie; Chen, Michael Z; Freed-Pastor, William A; McGinnis, Christopher S; Patterson, David M; Gartner, Zev J; Chow, Eric D; Bivona, Trever G; Chan, Michelle M; Yosef, Nir; Jacks, Tyler; Weissman, Jonathan S; ... Show more Show less
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Abstract
Tumor evolution is driven by the progressive acquisition of genetic and epigenetic alterations that enable uncontrolled growth and expansion to neighboring and distal tissues. The study of phylogenetic relationships between cancer cells provides key insights into these processes. Here, we introduced an evolving lineage-tracing system with a single-cell RNA-seq readout into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution. We found that the loss of the initial, stable alveolar-type2-like state was accompanied by a transient increase in plasticity. This was followed by the adoption of distinct transcriptional programs that enable rapid expansion and, ultimately, clonal sweep of stable subclones capable of metastasizing. Finally, tumors develop through stereotypical evolutionary trajectories, and perturbing additional tumor suppressors accelerates progression by creating novel trajectories. Our study elucidates the hierarchical nature of tumor evolution and, more broadly, enables in-depth studies of tumor progression.
Date issued
2022
URI
https://hdl.handle.net/1721.1/146823
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Cell
Publisher
Elsevier BV
Citation
Yang, Dian, Jones, Matthew G, Naranjo, Santiago, Rideout, William M, Min, Kyung Hoi Joseph et al. 2022. "Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution." Cell, 185 (11).
Version: Final published version

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