2014/12/11 by Jiguang Wang, Hossein Khiabanian, Davide Rossi +10 · 2 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Chronic Lymphocytic Leukemia Research #Genetic factors in colorectal cancer #Cancer Genomics and Diagnostics
paper · doi:10.7554/elife.02869
openalex publication_date 2014/12/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.