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Genetic instability 

Genetic instability
Chapter:
Genetic instability
Author(s):

Jennifer Wilding

and Walter Bodmer

DOI:
10.1093/med/9780199656103.003.0008
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date: 18 August 2019

Most cancers are thought to exhibit some form of genetic instability, which can either be at the nucleotide or chromosome level. It is tempting to speculate that because genetic instability accelerates the rate of accumulation of mutations, it would act as a necessary driving force for the development and progression of cancer, and there has been much debate as to whether there is an absolute requirement for genetic instability during tumorigenesis. Although the mechanism of the acquired genetic instability is clear in many germline cancer-predisposing syndromes, the molecular basis for genetic instability in sporadic cancers remains unclear. This chapter will give a very brief summary of the main features of the major DNA damage response and repair pathways, the germline mutations in genes within these pathways which predispose to cancers, and an overview of some of the possible mechanisms through which sporadic cancers may become genetically unstable.

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