Evolutionary Mechanisms and Diversity in Cancer

Heng, Henry H.Q.; Stevens, Joshua B.; Bremer, Steven W.; Guo, Liu; Abdallah, Batoul Y.; Ye, Christine J.

doi:10.1016/b978-0-12-387688-1.00008-9

Cited by 82 publications

(130 citation statements)

References 109 publications

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“…While most of the molecular targets are well-characterized, in real tumors, they quickly become moving targets under medical treatments, especially when the treatment pressure is high, rapid and massive genome reorganization (termed genome chaos) occurs, which can drastically change dominating pathways. [24][25][26] Interestingly, mathematical and evolutionary modeling have supported that therapeutic intervention can provide selective pressure for the expansion of resistant variants, 27,28 and treatment has been proposed to accelerate cancer genome evolution and tumor progression. 29 This would suggest that, regardless of which hallmark is targeted, the cancer adapts and persists.…”

Section: The Significance and Limitations Of Using The Hallmarks Of Cmentioning

confidence: 99%

“…1). 24,25 The transition of two phases of somatic cell evolution is linked to stress response, system instability, genome-mediated system replacement coupled with diverse phenotypes and how evolution occurs. Together with the evolutionary mechanism of cancer, it offers explanations to many previous puzzling issues, such as (i) why there is elevated genome alteration in the first place.…”

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

“…The genome serves as the selective entity and platform for gene interaction, which is much more powerful than individual gene mutations. One way cells can acquire such massive genome alterations, is through a phenomenon termed genome chaos, 25,26,49,50 also referred to as chromoplexy and chromothripsis. 37,38 This process, driven by both internal and external stressors, occurs within the punctuated phase and contributes to the diversity necessary for Current cytogenetics defines a clonal chromosome aberration (CCA) as a given chromosome aberration which can be detected at least twice within 20 to 40 mitotic figures, while a non-clonal chromosome aberration (NCCA) is observed at a frequency less than 4% (less than 2 in 50 mitotic cells examined).…”

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

“…In contrast to the traditional assumption that genome-level change would be passed on to the daughter cells if the cell divides, for these cells with unstable genomes, parental cells cannot pass on the same genome. 25,32,35,36 This leads to the unique feature of the cancer cell population, where an entire cell population can display different types of genomes.…”

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

“…To distinguish the cancer evolutionary process based on the contribution of genome or gene, and punctuated or stepwise pattern, we use macro-and micro-cellular evolution. 25,33,35,41 In the concept of species, individuals share the same karyotype. For individual cancer cells, they can or cannot share the same karyotype.…”

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

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Evolutionary mechanism unifies the hallmarks of cancer

Horne

Pollick

Heng

2014

Intl Journal of Cancer

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The basis for the gene mutation theory of cancer that dominates current molecular cancer research consists of: the belief that gene‐level aberrations such as mutations are the main cause of cancers, the concept that stepwise gene mutation accumulation drives cancer progression, and the hallmarks of cancer. The research community swiftly embraced the hallmarks of cancer, as such synthesis has supported the notions that common cancer genes are responsible for the majority of cancers and the complexity of cancer can be dissected into simplified molecular principles. The gene/pathway classification based on individual hallmarks provides explanation for the large number of diverse gene mutations, which is in contrast to the original estimation that only a handful of gene mutations would be discovered. Further, these hallmarks have been highly influential as they also provide the rationale and research direction for continued gene‐based cancer research. While the molecular knowledge of these hallmarks is drastically increasing, the clinical implication remains limited, as cancer dynamics cannot be summarized by a few isolated/fixed molecular principles. Furthermore, the highly heterogeneous genetic signature of cancers, including massive stochastic genome alterations, challenges the utility of continuously studying each individual gene mutation under the framework of these hallmarks. It is therefore necessary to re‐evaluate the concept of cancer hallmarks through the lens of cancer evolution. In this analysis, the evolutionary basis for the hallmarks of cancer will be discussed and the evolutionary mechanism of cancer suggested by the genome theory will be employed to unify the diverse molecular mechanisms of cancer.

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Section: The Significance and Limitations Of Using The Hallmarks Of Cmentioning

confidence: 99%

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

Section: Genome Theory Of Cancer Evolution Offers a Genome System Appmentioning

confidence: 99%

See 3 more Smart Citations

Evolutionary mechanism unifies the hallmarks of cancer

Horne

Pollick

Heng

2014

Intl Journal of Cancer

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Chromosomal Instability ( CIN ) in Cancer

Horne

Heng

2015

Encyclopedia of Life Sciences

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Chromosomal instability ( CIN ) represents a common feature in the majority of cancers. Despite that the search for specific molecular mechanisms linked to the causation or consequences of cancer has become very popular in cancer research, there is no general conceptual framework that unifies the observed diverse molecular findings. By applying the genome theory of cancer evolution, we briefly define and clarify CIN , synthesise its importance in macro‐cellular evolutionary selection, unify diverse molecular mechanisms under the evolutionary mechanism of cancer and discuss its potential implications. Understanding the relationship of stress, CIN and genome‐mediated cancer evolution offers clarity and direction to researchers, and monitoring CIN within an evolutionary context can provide valuable clinical information for determining treatment administration and patient prognosis. Key Concepts Chromosomal aberrations exist in the majority of cancers, suggesting the importance of understanding CIN in cancer. Cancer genome evolution exists in two cyclical phases: a genome replacement mediated punctuated (macro‐cellular) phase and a gene/epigene‐mediated stepwise (micro‐cellular) phase; triggering CIN is the key to entering the macro‐cellular evolutionary phase. CIN represents the key driver of cancer, as high levels rapidly produce wide varieties of new genome systems, providing necessary heterogeneity (and ample opportunity) for evolutionary selection. Understanding the relationship among CIN, different genetic level dynamics and macro‐cellular evolution can be accomplished using multiple level landscape models. Application of the evolutionary mechanism of cancer in understanding CIN offers clarity by unifying the wide variety of involved genetic and non‐genetic mechanisms and factors. The consequences of high stress‐induced CIN (e.g. genome chaos, adaptation and accelerated macro‐cellular evolution) hold high implications in cancer treatment and drug resistance. Fuzzy inheritance, which also reflects as elevated CIN at the genome level, represents a major mechanism of cancer evolution. Monitoring CIN within an evolutionary context can provide valuable information for both cancer research and treatment.

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Somatic Genome Variations

Iourov

Vorsanova²,

Yurov

2012

Encyclopedia of Life Sciences

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The genome of somatic cells is susceptible to change through ontogeny. These variations can take a variety of forms and occur through different mechanisms. Stochastic intercellular variations of the genome are suggested to be involved in a number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging). However, somatic genome variations have been shown to be involved in pathogenesis of a broad spectrum of human diseases (from chromosomal and monogenic diseases to complex disorders). Nonetheless, the contribution of somatic genome variations to human biodiversity and disease is usually underappreciated. The latter is due to consistent questioning the possibility of techniques used for uncovering somatic genome variation. Therefore, technological aspects of studying intercellular variation of the human genome remain an additional important issue for understanding the role of somatic mosaicism in health and disease. Key Concepts: The cellular genome is highly variable both at molecular and at chromosomal level. Somatic variation of the human genome is a likely mechanism for biodiversity either at intercellular or at interindividual level. A number of critical biological processes (pre‐natal development, cell number regulation, cell death and aging) seem to be mediated by somatic genome variations. According to current concepts, the commonest type of intercellular genome variations are those manifested as changes of chromosome numbers (aneuploidy or polyploidy). Somatic genome variations are known to contribute to pathogenesis of hereditary and chromosomal diseases. Intercellular genome variation is a highly probable mechanism of complex disorders (i.e. diseases of the brain and immune system), pre‐natal mortality and cancer. Understanding of the way to uncover somatic genome variations is an important issue for determining the contribution to intercellular/interindividual diversity in health and disease as well as their functional consequences.

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Evolutionary Mechanisms and Diversity in Cancer

Cited by 82 publications

References 109 publications

Evolutionary mechanism unifies the hallmarks of cancer

Evolutionary mechanism unifies the hallmarks of cancer

Chromosomal Instability ( CIN ) in Cancer

Somatic Genome Variations

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