Genetics and genetic instability in cancer

"The Integrity"of the human genome is under continual threat from endogenous and exogenous mutagens, and as a result of errors introduced during DNA replication. As the lesions generated by these processes, if left uncorrected, may lead to deleterious mutations, cells employ several sophisticated mechanisms to both prevent and repair such genomic damage. Failure of these repair mechanisms, leading to genomic instability, is common in cancer, and has even been suggested to be a universal characteristic of malignancy. This chapter outlines these cellular processes and reviews the both the mechanisms and consequences of their dysregulation in human cancer. It also highlights the emerging evidence suggesting that genomic instability is an important determinant of tumour behaviour. Finally, it discusses the possibility that targeting genomic instability may benefit patients with genomically unstable tumours in the clinic.