Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia
- Columbia University, United States
- Amedeo Avogadro University of Eastern Piedmont, Italy
- Centro di Riferimento Oncologico, Italy
- University of Southampton, United Kingdom
- Catholic University of the Sacred Heart, Italy
- University of Modena and Reggio Emilia, Italy
- Tor Vergata University, Italy
- Sapienza University, Italy
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.
Article and author information
Author details
Reviewing Editor
- Emmanouil T Dermitzakis, University of Geneva Medical School, Switzerland
Ethics
Human subjects: The study was approved by the institutional ethical committee of the Azienda Ospedaliero-Universiataria Maggiore della Carita di Novara affiliated with the Amedeo Avogadro University of Eastern Piedmont, Novara, Italy (Protocol Code 59/CE; Study Number CE 8/11). Patients provided informed consent in accordance with local IRB requirements and Declaration of Helsinki
Version history
- Received: March 24, 2014
- Accepted: December 10, 2014
- Accepted Manuscript published: December 11, 2014 (version 1)
- Version of Record published: January 28, 2015 (version 2)
Copyright
© 2014, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia
eLife 3:e02869.
https://doi.org/10.7554/eLife.02869
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