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Modeling Evolutionary Dynamics of Epigenetic Mutations in Hierarchically Organized Tumors

Andrea Sottoriva, Louis Vermeulen, Simon Tavaré, Philip E. Bourne
2011 PLoS Computational Biology  
Our results demonstrate that epigenetic mutations that occur during mitosis display highly altered dynamics in CSC-driven malignancies compared to a classical, non-hierarchical model of growth.  ...  In this study we use a novel cellular Potts model to elucidate the dynamics of established malignancies that are driven by a small subset of CSCs.  ...  To study the difference between the two models in term of evolutionary dynamics, we now consider non-neutral epigenetic mutations that confer changes in terms of cell fitness.  ... 
doi:10.1371/journal.pcbi.1001132 pmid:21573198 pmcid:PMC3088646 fatcat:p55kenoizjespaixdzct7orrri

New Concepts of Germline Gene –reactivated Cancer

Yue Zhang
2011 Human Genetics & Embryology  
The "wild type" epigenetic landscape has been carefully shaped over evolutionary time to establish distinct cell fate lineages, and that the tumor has maintained some of this developmental architecture  ...  The mechanism that ectopic expression of germline genes result in somatic tumors such as melanoma and brain tumors remains a big challenge [1, 2] .  ...  Hisashi Moriguchi for his discussion on tumorgenicity of induced pluripotent cells (iPS) and share unpublished data for chemicals iPS to reprogramming cancerous cells  ... 
doi:10.4172/2161-0436.1000e101 fatcat:ufn26pbkhnhivebwrhptxqtkuq

DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors

Tali Mazor, Aleksandr Pankov, Brett E. Johnson, Chibo Hong, Emily G. Hamilton, Robert J.A. Bell, Ivan V. Smirnov, Gerald F. Reis, Joanna J. Phillips, Michael J. Barnes, Ahmed Idbaih, Agusti Alentorn (+9 others)
2015 Cancer Cell  
Phyloepigenetics recapitulates the phylogenetics of tumor evolution d Robust model of gliomagenesis from tumor initiation through malignant progression SUMMARY The evolutionary history of tumor cell populations  ...  This study suggests strong interdependency of genetic and epigenetic alterations in these human brain tumors.  ...  Johnson for assistance with mutation validation, N. Jabado and S. Papillon-Cavanagh for providing raw data for methylation analysis, and K.  ... 
doi:10.1016/j.ccell.2015.07.012 pmid:26373278 pmcid:PMC4573399 fatcat:sna42g2frrdjfiiisxcdrvwfqa

Evolving concepts of tumor heterogeneity

Victoria R Zellmer, Siyuan Zhang
2014 Cell & Bioscience  
This evolutionary model of tumorigenesis has largely been shaped by seminal reports of fitness-promoting mutations conferring a malignant cellular phenotype.  ...  In this review, we seek to summarize major milestones in tumor evolution, identify key aspects of tumor heterogeneity in a TME-dependent evolutionary context, and provide insights on the clinical challenges  ...  S.Z. is a Nancy Dee Assistant Professor in Cancer Research at the University of Notre Dame and Harper Cancer Research Institute.  ... 
doi:10.1186/2045-3701-4-69 pmid:25937891 pmcid:PMC4417538 fatcat:ki7wxdds5bg67e733gdwkjye2i

Evolution of the Cancer Stem Cell Model

Antonija Kreso, John E. Dick
2014 Cell Stem Cell  
Although often considered as mutually exclusive models to describe tumor heterogeneity, we propose that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity  ...  However, it is becoming increasingly clear that cancer cells display features of normal tissue organization, where cancer stem cells (CSCs) can drive tumor growth.  ...  Anders for critical discussions and review of this review article.  ... 
doi:10.1016/j.stem.2014.02.006 pmid:24607403 fatcat:vycfcw5robfgbobdi3xenqvsfe

Structure of Intratumor Heterogeneity: Is Cancer Hedging Its Bets? [article]

B. Brutovsky, D. Horvath
2013 arXiv   pre-print
Although it is agreed that intratumor heterogeneity increases probability of the emergence of therapy resistant clones, more instructive role of its structure in the process of cancer dynamics and metastasis  ...  In the paper, intratumor heterogeneity is viewed as a product of two, in general stochastic, processes, evolutionary optimization and changing environment, respectively.  ...  If epigenetic landscape, due to genetic mutations or tumor microenvironment, changes, probability of the cell finding itself in cancerous attractors may increase [77] .  ... 
arXiv:1307.0607v1 fatcat:wntlg4ttfncqtlzs5d3fyhn3i4

An Evolutionary Approach to Clonally Complex Hematologic Disorders

Emily Schwenger, Ulrich Steidl
2021 Blood Cancer Discovery  
Here, we review the evidence both within the hematologic malignancy field and also borrow from perspectives rooted in evolutionary biology to reframe pathogenesis of hematologic disorders as dynamic processes  ...  Former models of cell-intrinsic clonal dominance driven by acquisition of driver genes in a stereotypic sequence are often insufficient in explaining observations such as clonal hematopoiesis, and new  ...  Acknowledgments The authors acknowledge Katie Vicari for her expertise in design of the figures presented in this review. E. Schwenger would like to thank Drs.  ... 
doi:10.1158/2643-3230.bcd-20-0219 pmid:34027415 pmcid:PMC8133502 fatcat:azo3n3zpzffpdguj737xhosshy

Computational Cancer Biology: An Evolutionary Perspective

Niko Beerenwinkel, Chris D. Greenman, Jens Lagergren, Ruth Nussinov
2016 PLoS Computational Biology  
Much of evolutionary modeling in general, and of cancer in particular, has remained conceptual or qualitative, either because of strong simplifications in the interest of mathematical tractability or lack  ...  Analogous to other evolutionary studies, mathematical modeling will be key to the success of understanding the somatic evolution of cancer [2] .  ...  The meeting served as a starting point and source of inspiration for this work.  ... 
doi:10.1371/journal.pcbi.1004717 pmid:26845763 pmcid:PMC4742235 fatcat:zspm3avnovekflm5b5vmokgfjq

Cancer: evolutionary, genetic and epigenetic aspects

Anatoly V. Lichtenstein
2010 Clinical Epigenetics  
Recent data on genetic and epigenetic mechanisms of cell transformation summarized in this review support the latter point of view, namely that carcinogenesis is an evolutionary conserved phenomenona programmed  ...  The essence of the second resides in the question "Does cancer kill the individual and save the species?" (Sommer, Hum Mutat 3: [166][167][168][169] 1994).  ...  Conflict of interest The author declares that he has no conflict of interest.  ... 
doi:10.1007/s13148-010-0010-6 pmid:22704202 pmcid:PMC3365664 fatcat:kpjoqjucvbb6zbcbu5zv4jso5u

Breast cancer intra-tumor heterogeneity

Luciano G Martelotto, Charlotte KY Ng, Salvatore Piscuoglio, Britta Weigelt, Jorge S Reis-Filho
2014 Breast Cancer Research  
Burgeoning genetic, epigenetic and phenomenological data support the existence of intra-tumor genetic heterogeneity in breast cancers; however, its basis is yet to be fully defined.  ...  Here we review the models that explain tumor heterogeneity, the causes of intra-tumor genetic diversity and their impact on our understanding and management of breast cancer, methods to study intra-tumor  ...  organization of cancer cells, the clonal evolution model explains intra-tumor diversity as speciation by natural selection and does not rely on a hierarchical model.  ... 
doi:10.1186/bcr3658 pmid:25928070 pmcid:PMC4053234 fatcat:mvrxuysdxjhfjhggn2od7xlc4a

Evolutionary biology of cancer

Bernard Crespi, Kyle Summers
2005 Trends in Ecology & Evolution  
We describe here how recent evolutionary ecological studies have elucidated the roles of predation by the immune system and competition among normal and cancerous cells in the somatic evolution of cancer  ...  We discuss how applications of the tools of ecology and evolutionary biology are poised to revolutionize our understanding and treatment of this disease.  ...  The somatic evolutionary dynamics of tumor suppressor gene inactivation have recently been modelled by Komarova et al. [64] and Nowak et al.  ... 
doi:10.1016/j.tree.2005.07.007 pmid:16701433 fatcat:4fkyo6hyxbhgbpz44uo2amf2yu

Cancer Stem Cell Tumor Model Reveals Invasive Morphology and Increased Phenotypical Heterogeneity

A. Sottoriva, J. J.C. Verhoeff, T. Borovski, S. K. McWeeney, L. Naumov, J. P. Medema, P. M.A. Sloot, L. Vermeulen
2010 Cancer Research  
In addition, we provide evidence that the CSC model is accompanied by highly altered evolutionary dynamics compared with the ones predicted to exist in a stochastic, nonhierarchical tumor model.  ...  This research shows that the hierarchical organization of malignant clones, as advocated in the CSC concept, has major implications for tumor biology.  ...  The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.  ... 
doi:10.1158/0008-5472.can-09-3663 pmid:20048071 fatcat:yehoeecm4ffj7fxs7ndvkcm36u

Intratumor Heterogeneity: Novel Approaches for Resolving Genomic Architecture and Clonal Evolution

Ravi G. Gupta, Robert A. Somer
2017 Molecular Cancer Research  
Dynamic evolutionary models may explain how these populations grow within the ecosystem of tissues, including linear, branching, neutral, and punctuated patterns.  ...  Recent evidence in breast cancer favors branching and punctuated evolution driven by genome instability as well as nongenetic sources of heterogeneity, such as epigenetic variation, hierarchal tumor cell  ...  Evolutionary dynamics in cancer In the 1970s, Peter Nowell first proposed an evolutionary framework for carcinogenesis and described tumor progression in terms of the evolution of a single increasingly  ... 
doi:10.1158/1541-7786.mcr-17-0070 pmid:28596419 fatcat:nyfrmxfskzfj7pdhwjufjdmpdm

Cancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance

Hariharan Easwaran, Hsing-Chen Tsai, Stephen B. Baylin
2014 Molecular Cell  
In this review, we discuss the possible role of epigenetic abnormalities, as well as genetic alterations in such dynamics, and in the creation of cellular heterogeneity in cancers of all types.  ...  The existence of sub-populations of cells in cancers with increased tumor initiating capacities and self-renewal potential, often termed 'cancer stem cells', is a much discussed and key area of cancer  ...  Acknowledgments Portions of the authors' writing is supported by National Cancer institute (NCI) CA043318, National Institutes of Environmental Health Sciences (NIEHS) ES011858, National Institutes of  ... 
doi:10.1016/j.molcel.2014.05.015 pmid:24905005 pmcid:PMC4103691 fatcat:55gx7k2zzfdnxcf6ahfrel6xai

Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias

Matthieu Duchmann, Lucie Laplane, Raphael Itzykson
2021 Cancers  
clonal emergence (mutation rate, number of generations, and effective size of the leukemic population) and the causes of clonal dynamics.  ...  Acute myeloid leukemias (AML) results from the accumulation of genetic and epigenetic alterations, often in the context of an aging hematopoietic environment.  ...  If we apply to cancer the conceptual framework of evolutionary dynamics in asexual organisms, most of which has been fueled by experiments on bacteria, we can predict that the mutational rate, the number  ... 
doi:10.3390/cancers13194887 pmid:34638371 fatcat:yqqt7ixix5edrfkj64wjeujdca
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