Preface

Heng, Henry H.Q.

doi:10.1159/000347035

Cited by 5 publications

(1 citation statement)

References 19 publications

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“…Some known complications include: a) most cancer cases display non-clonal aneuploidy (impeding the fact that clonal aneuploidy has been much more commonly researched for decades) [ 5 – 9 ], b) aneuploidy often occurs in combination with other types of genetic/epigenetic and genomic aberrations (translocations and polyploidy) (Table 2 ) c) there is often a variable degree of somatic mosaicism [ 10 – 13 ], and d) there is a complex, dynamic relationship between aneuploidy and genome instability (Table 3 ). Interestingly, many common and complex diseases have been linked to non-clonal aneuploidy and somatic mosaicism as well [ 14 , 15 ], which has led to efforts to search for commonly shared mechanisms among different diseases or illness conditions [ 16 – 19 ]. It is worth noting that aneuploidy can also be detected from the normal developmental process [ 20 – 22 ].…”

Section: Background and Progressmentioning

confidence: 99%

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Regan

Guo

et al. 2018

Mol Cytogenet

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BackgroundIn the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays the key role in cancer. As the molecular characterization of the causes and effects of aneuploidy progresses, the search for the general mechanism of how aneuploidy contributes to cancer becomes increasingly challenging: since aneuploidy can be linked to diverse molecular pathways (in regards to both cause and effect), the chances of it being cancerous is highly context-dependent, making it more difficult to study than individual molecular mechanisms. When so many genomic and environmental factors can be linked to aneuploidy, and most of them not commonly shared among patients, the practical value of characterizing additional genetic/epigenetic factors contributing to aneuploidy decreases.ResultsBased on the fact that cancer typically represents a complex adaptive system, where there is no linear relationship between lower-level agents (such as each individual gene mutation) and emergent properties (such as cancer phenotypes), we call for a new strategy based on the evolutionary mechanism of aneuploidy in cancer, rather than continuous analysis of various individual molecular mechanisms. To illustrate our viewpoint, we have briefly reviewed both the progress and challenges in this field, suggesting the incorporation of an evolutionary-based mechanism to unify diverse molecular mechanisms. To further clarify this rationale, we will discuss some key concepts of the genome theory of cancer evolution, including system inheritance, fuzzy inheritance, and cancer as a newly emergent cellular system.ConclusionIllustrating how aneuploidy impacts system inheritance, fuzzy inheritance and the emergence of new systems is of great importance. Such synthesis encourages efforts to apply the principles/approaches of complex adaptive systems to ultimately understand aneuploidy in cancer.

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Section: Background and Progressmentioning

confidence: 99%

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Regan

Guo

et al. 2018

Mol Cytogenet

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Heterogeneity Mediated System Complexity: The Ultimate Challenge for Studying Common and Complex Diseases

Heng

Horne

Stevens

et al. 2016

The Value of Systems and Complexity Sciences for Healthcare

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Chromosomal instability (CIN): what it is and why it is crucial to cancer evolution

Heng

Bremer

Stevens

et al. 2013

Cancer Metastasis Rev

169

180

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Results of various cancer genome sequencing projects have "unexpectedly" challenged the framework of the current somatic gene mutation theory of cancer. The prevalence of diverse genetic heterogeneity observed in cancer questions the strategy of focusing on contributions of individual gene mutations. Much of the genetic heterogeneity in tumors is due to chromosomal instability (CIN), a predominant hallmark of cancer. Multiple molecular mechanisms have been attributed to CIN but unifying these often conflicting mechanisms into one general mechanism has been challenging. In this review, we discuss multiple aspects of CIN including its definitions, methods of measuring, and some common misconceptions. We then apply the genome-based evolutionary theory to propose a general mechanism for CIN to unify the diverse molecular causes. In this new evolutionary framework, CIN represents a system behavior of a stress response with adaptive advantages but also serves as a new potential cause of further destabilization of the genome. Following a brief review about the newly realized functions of chromosomes that defines system inheritance and creates new genomes, we discuss the ultimate importance of CIN in cancer evolution. Finally, a number of confusing issues regarding CIN are explained in light of the evolutionary function of CIN.

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Preface

Abstract: No abstract available

Cited by 5 publications

References 19 publications

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems

Heterogeneity Mediated System Complexity: The Ultimate Challenge for Studying Common and Complex Diseases

Chromosomal instability (CIN): what it is and why it is crucial to cancer evolution

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