Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution
Name
1-s2.0-S0092867422004627-main.pdf
Description
Published version
Size
12.61 MB
Format
Adobe PDF
Checksum (MD5)
b95b16689c3cd1a4a1ad69861e80ee11
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
Date Issued
2022
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
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2022.04.015
