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Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia.

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 - Elife (2014)

Bottom Line: 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.Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Informatics, Columbia University, New York, United States.

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.

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Related in: MedlinePlus

Relative timing of mutations of 70 patients.Each column represents one patient with at least two time points. Magenta (MCF>5%, present) and blue bars (absent), which are ordered by time information, indicate the mutation status of the corresponding alteration. For one patient, if the present of alteration A is earlier than B, we claim A predates B.
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fig11: Relative timing of mutations of 70 patients.Each column represents one patient with at least two time points. Magenta (MCF>5%, present) and blue bars (absent), which are ordered by time information, indicate the mutation status of the corresponding alteration. For one patient, if the present of alteration A is earlier than B, we claim A predates B.

Mentions: In our work, the relative timing of mutations is inferred by longitudinal data with multiple time points. If the presence of mutation A (allele fraction >5%) predates that of mutation B, mutation A is considered earlier than mutation B (Author response image 5).Author response image 6.Phylogenetic trees of CLL patients.


Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia.

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 - Elife (2014)

Relative timing of mutations of 70 patients.Each column represents one patient with at least two time points. Magenta (MCF>5%, present) and blue bars (absent), which are ordered by time information, indicate the mutation status of the corresponding alteration. For one patient, if the present of alteration A is earlier than B, we claim A predates B.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308685&req=5

fig11: Relative timing of mutations of 70 patients.Each column represents one patient with at least two time points. Magenta (MCF>5%, present) and blue bars (absent), which are ordered by time information, indicate the mutation status of the corresponding alteration. For one patient, if the present of alteration A is earlier than B, we claim A predates B.
Mentions: In our work, the relative timing of mutations is inferred by longitudinal data with multiple time points. If the presence of mutation A (allele fraction >5%) predates that of mutation B, mutation A is considered earlier than mutation B (Author response image 5).Author response image 6.Phylogenetic trees of CLL patients.

Bottom Line: 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.Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Informatics, Columbia University, New York, United States.

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.

Show MeSH
Related in: MedlinePlus