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Telomeres in cancer: tumour suppression and genome instability

2017; Nature Portfolio; Volume: 18; Issue: 3 Linguagem: Inglês

10.1038/nrm.2016.171

1471-0080

John Maciejowski, Titia de Lange,

Cancer Research and Treatments

Telomere shortening and loss of telomere protection can have a tumour-suppressive effect by mediating proliferation arrest. Ultimately, however, these processes can cause a state of extensive genome instability known as telomere crisis, which can facilitate tumorigenesis by causing oncogenic chromosomal rearrangements, including chromothripsis, kataegis and tetraploidization. The shortening of human telomeres has two opposing effects during cancer development. On the one hand, telomere shortening can exert a tumour-suppressive effect through the proliferation arrest induced by activating the kinases ATM and ATR at unprotected chromosome ends. On the other hand, loss of telomere protection can lead to telomere crisis, which is a state of extensive genome instability that can promote cancer progression. Recent data, reviewed here, provide new evidence for the telomere tumour suppressor pathway and has revealed that telomere crisis can induce numerous cancer-relevant changes, including chromothripsis, kataegis and tetraploidization.