Cancer Genomics

Cell Fate in Cancer

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The cell is the basic unit of life. The attainment of a nucleus to house the genetic material is thought to have provided a distinct advantage to the evolving cell, ultimately allowing the emergence of differentiated, specialized cells.  Hoarding evidence suggests that genomes are organized non-randomly into complex 3D configurations that vary according to cell type, stage of development, differentiation and disease status. The principles, which guide higher order organization, the mechanisms responsible for establishment, maintenance and alterations of higher order genome, and the functional consequences of aberrant genome and nuclear organization, have become zones of intense interest. The higher-order spatial and temporal organization of genomes in the cell nucleus is rapidly evolving as a driver of biological function in differentiation, development and disease and the incorporation of information on higher order genome organization add an additional level of complexity in our understanding of genome regulation.  DNA sequence variations and biochemical sequence modifications co-define cell fate. Through exploration of cancer genomes, new gene categories have been identified that imply novel underlying mechanisms related to epigenetics, transcriptional processes and cell differentiation. These contrivances are of major prominence in tumorigenesis and cancer therapy failure.

Differentiated tumor cells may present different elevated cell potencies. Thus, tumor heterogeneity may be presented as a certain three-dimensional space that is defined by the range of three key features – cell potency, cell lineage specificity and variance. Cell fate dynamics and the resulting cell population diversity and evolution during tumorigenesis and cancer drug treatment have been correlated with cellular responses to environmental stress. This might provide new insights for understanding tumorigenesis and new strategies that target whole cell system dynamics for cancer therapy.