Abstract
Genome stability is tightly regulated through the cell cycle. Aberrations in genome structure and sequence are a hallmark of malignancy and these changes can allow abnormal cells to escape the regulatory mechanisms that would otherwise direct these cells into apoptosis or senescence. When genome instability occurs, it can happen as large or small structural changes in the genome, changes in gene expression, or even changes at the epigenetic level. There are many environmental factors that can induce DNA damage and strain the machinery that is responsible for maintaining genome stability. In some cases, such as UV light or chemical carcinogens, it is possible to avoid these factors and thus reduce the risk of cancer. But, in other instances, hereditary mutations impair the function of genes and their products, which normally protect the stability of the genome. While genomic instability offers selective advantages to the tumor, the tumor-specific loss of these pathways may provide therapeutic opportunities, which could be personalized through knowledge of the specific types of genomic instability that characterize an individual’s tumor.
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Abbreviations
- BER:
-
Base excision repair
- BFB:
-
Break fusion break
- CDK:
-
Cyclin dependent kinase
- CGH:
-
Comparative genomic hybridization
- CIN:
-
Chromosome instability
- CpG:
-
C-phosphate-G
- CRC:
-
Colorectal cancer
- DDR:
-
DNA damage response
- DNA:
-
Deoxynucleic acid
- DSB:
-
Double strand break
- EMT:
-
Epithelial to mesenchymal transition
- HDR:
-
Homology directed repair
- LOH:
-
Loss of heterozygosity
- MET:
-
Mesenchymal to epithelial transition
- MIN or MSI,:
-
Microsatellite instability
- MMR:
-
Mismatch repair
- mtDNA:
-
Mitochondrial DNA
- NER:
-
Nucleotide excision repair
- NHEJ:
-
Non-homologous end joining
- NIN:
-
Nucleotide instability
- PCR:
-
Polymerase chain reaction
- SAC:
-
Spindle assembly checkpoint
- UV:
-
Ultraviolet
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Acknowledgements
CAM is supported through a CIHR New Investigator Salary award while HC and MC are supported through a Michael Cuccione Foundation for Childhood Cancer Research scholarship and fellowship, respectively.
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Chen, H., Maxwell, C., Connell, M. (2015). The Generation, Detection, and Prevention of Genomic Instability During Cancer Progression and Metastasis. In: Maxwell, C., Roskelley, C. (eds) Genomic Instability and Cancer Metastasis. Cancer Metastasis - Biology and Treatment, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-12136-9_2
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