Limits...
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.

Show MeSH

Related in: MedlinePlus

Definition of mutation cell frequency.MAF: mutation allele frequency; MCF: mutation cell frequency. The black lines within the circles represent DNA copies, and the crosses represent mutations. The contingent table shows the difference between MAF and MCF.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4308685&req=5

fig7: Definition of mutation cell frequency.MAF: mutation allele frequency; MCF: mutation cell frequency. The black lines within the circles represent DNA copies, and the crosses represent mutations. The contingent table shows the difference between MAF and MCF.

Mentions: This is a good suggestion. To consider potential bias caused by copy number abnormalities, we introduce mutation cell frequency (MCF) instead of Mutation Allele Frequency (MAF). As shown in Author response image 1, MCF represents the fraction of cells containing alterations. Different from MAF, MCF of a mutation is not affected by copy numbers. To infer MCF of different types of alterations, we apply the following strategy:


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)

Definition of mutation cell frequency.MAF: mutation allele frequency; MCF: mutation cell frequency. The black lines within the circles represent DNA copies, and the crosses represent mutations. The contingent table shows the difference between MAF and MCF.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Definition of mutation cell frequency.MAF: mutation allele frequency; MCF: mutation cell frequency. The black lines within the circles represent DNA copies, and the crosses represent mutations. The contingent table shows the difference between MAF and MCF.
Mentions: This is a good suggestion. To consider potential bias caused by copy number abnormalities, we introduce mutation cell frequency (MCF) instead of Mutation Allele Frequency (MAF). As shown in Author response image 1, MCF represents the fraction of cells containing alterations. Different from MAF, MCF of a mutation is not affected by copy numbers. To infer MCF of different types of alterations, we apply the following strategy:

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