Genomic instability has been an area of active area of research in the last two decades. Based on the initial study for hereditary cancers, DNA repair gene family mutations have been identified. In sporadic (non-hereditary) cancers, several large-scale DNA sequencing studies suggest that mutations in DNA repair genes are less frequent, suggesting the complexity of tumorigenesis of sporadic cancers. So far, several important genes have been identified, by using mostly cell line models and mice studies. These include DNA damage response modifier like ataxia telangiectasia mutated (ATM), conventional tumor suppressor genes like TP53 and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF). Various hypotheses for sporadic tumorigenesis have been developed, and so far, “oncogene-induced DNA replication stress model” has been gaining widespread interests. In this review, we will first describe some of the important concepts of genomic instability. Then, we will outline oncogene-induced genomic instability and discuss the role of the MYC gene during this process, which will be followed by detailed reviews of mutation data. We hope that this review can outline the overall perspectives of genomic instability.
Impact statement
This review provides various genetic and cell line data previously published in a way to explain how cellular stress can lead into genetic instability.
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