@article{56,
  keywords = {fitness, genetically engineered mouse model, lineage tracing, lung cancer, phylogenetics, plasticity, single cell, transcriptome heterogeneity, tumor evolution},
  author = {Dian Yang and Matthew Jones and Santiago Naranjo and William Rideout and Kyung Min and Raymond Ho and Wei Wu and Joseph Replogle and Jennifer Page and Jeffrey Quinn and Felix Horns and Xiaojie Qiu and Michael Chen and William Freed-Pastor and Christopher McGinnis and David Patterson and Zev Gartner and Eric Chow and Trever Bivona and Michelle Chan and Nir Yosef and Tyler Jacks and Jonathan Weissman},
  title = {Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution.},
  abstract = {<p>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.</p>},
  year = {2022},
  journal = {Cell},
  volume = {185},
  pages = {1905-1923.e25},
  month = {05/2022},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2022.04.015},
  language = {eng},
}