Carcinogenesis is thought to originate from a single cell which accumulates a series of well-defined, albeit randomly obtained, genefic mutafions, leading to carcinogenic transformation. Despite the inroads into elucidafing the carcinogenesis process, there sfill remain gaps in our understanding of how mutafions drive cell transformation and subsequent cancer progression. Although gene mutations cleariy contribute to cancer, no single mutated gene or combination of mutated genes occur in all or even the majority of cancers. Moreover, as Vogelstein and K nz er {Nature Rev Cancer 2004) point out, it is not gene mutafions, but primarily chromosome-level aberrations that cells exhibit following transformafion to the cancer state. Although it has long been assumed that cancers arise from mutated differentiated cells, mutated stem cells are now also considered candidate cancer precursors due to their self-renewal and differentiafion capacity. Although genomic instability is ubiquitous across malignant cancers, its mechanisfic underpinnings remain unclear. Inhibifion of stability genes, alterafions in mitosis genes, aberrant centrosomes, aneuploidy, telomere dysregulafions and, for virus-linked cancers, virus-induced fusion of genefically-mutated cells, are all candidate causes ofthe instability. Given that gene mutafions and particulariy chromosome aberrations decrease the fitness of a cell, how is it that cancer cell populations are able to sustain and proliferate in the face of the high degree of chromosomal damage per cell? If the answer lies in the existence of cancer stem cells, one needs to ask how this privileged cell compartment is itself exempt from the deleterious effects of chromosomal damage.
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