Chromosomal Instability, Aneuploidy, and Cancer
Most human neoplasms are aneuploid and this state of abnormal chromosome number is the result of elevated rates of whole-chromosome mis-segregation, a process known as Chromosomal Instability (CIN). A number of cellular mechanisms that lead to CIN have recently been uncovered and it is now evident that CIN can result from the perturbation of a variety of pathways that normally ensure the faithful segregation of chromosomes during mitosis. Furthermore, some recent evidence is now linking chromosome mis-segregation to increased rates of DNA damage, as well as chromosome pulverization and endo-duplication. Despite of the advances made to understand the cause of CIN in experimental models, the extent to which these basic mechanisms manifest themselves in human cancer remains poorly understood.
Acquiring an understanding of how CIN arises in cancer cells has also provided some preliminary tools to evaluate the role of CIN in tumor initiation, growth and how chromosome mis-segregation influences prognosis and resistance or response to therapy. Just like DNA mutation, it is now apparent that the relationship between the frequency of chromosome mis-segregation and tumor behavior is not linear and that CIN may differentially influence tumor prognosis, evolution, and response to treatment in a context-dependent manner. Exploring the role of chromosomal imbalance in tumor evolution has the potential to uncover a major mechanism of tumor cell heterogeneity that affects the clonal evolution of cancer cells during tumorigenesis and tumor growth.
In this Frontiers Research Topic, we propose to create an interactive forum for reporting and discussing research efforts that pertain to the mechanisms of CIN and its effect on tumor initiation, growth, and evolution. We encourage submission of basic, translational and clinical research papers as well as hypothesis and theory articles and reviews. We also encourage work on non-cancer systems or other model organisms if it has a clear implication on our understanding of CIN and its effect on cellular adaptation.
Journal of Genomics & Gene Study