Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia

Jiguang Wang, Hossein Khiabanian, Davide Rossi, Giulia Fabbri, Valter Gattei, Francesco Forconi, Luca Laurenti, Roberto Marasca, Giovanni Del Poeta, Robin Foà, Laura Pasqualucci, Gianluca Gaidano, Raul Rabadan

Research output: Contribution to journalArticle

Abstract

Cancer is a clonal evolutionary process, caused by successive accumulation of genetic alterations providing milestones of tumor initiation, progression, dissemination, and/or resistance to certain therapeutic regimes. To unravel these milestones we propose a framework, tumor evolutionary directed graphs (TEDG), which is able to characterize the history of genetic alterations by integrating longitudinal and cross-sectional genomic data. We applied TEDG to a chronic lymphocytic leukemia (CLL) cohort of 70 patients spanning 12 years and show that: (a) the evolution of CLL follows a time-ordered process represented as a global flow in TEDG that proceeds from initiating events to late events; (b) there are two distinct and mutually exclusive evolutionary paths of CLL evolution; (c) higher fitness clones are present in later stages of the disease, indicating a progressive clonal replacement with more aggressive clones. Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

Original languageEnglish
JournaleLife
Volume3
DOIs
Publication statusPublished - 2014

Keywords

  • chronic lymphocytic leukemia
  • evolutionary biology
  • genomics
  • human
  • human biology
  • medicine
  • next generation sequencing
  • tumor evolutionary

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Wang, J., Khiabanian, H., Rossi, D., Fabbri, G., Gattei, V., Forconi, F., Laurenti, L., Marasca, R., Del Poeta, G., Foà, R., Pasqualucci, L., Gaidano, G., & Rabadan, R. (2014). Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia. eLife, 3. https://doi.org/10.7554/eLife.02869