Review

Nature Reviews Molecular Cell Biology 11, 220-228 (March 2010) | doi:10.1038/nrm2858

Focus on: Genome Instability

Genomic instability — an evolving hallmark of cancer

Simona Negrini1, Vassilis G. Gorgoulis2 & Thanos D. Halazonetis1,3  About the authors

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Genomic instability is a characteristic of most cancers. In hereditary cancers, genomic instability results from mutations in DNA repair genes and drives cancer development, as predicted by the mutator hypothesis. In sporadic (non-hereditary) cancers the molecular basis of genomic instability remains unclear, but recent high-throughput sequencing studies suggest that mutations in DNA repair genes are infrequent before therapy, arguing against the mutator hypothesis for these cancers. Instead, the mutation patterns of the tumour suppressor TP53 (which encodes p53), ataxia telangiectasia mutated (ATM) and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF) support the oncogene-induced DNA replication stress model, which attributes genomic instability and TP53 and ATM mutations to oncogene-induced DNA damage.

Author affiliations

  1. Department of Molecular Biology, CH-1205 Geneva, Switzerland.
  2. Department of Biochemistry, University of Geneva, CH1205 Geneva, Switzerland.
  3. Department of Histology and Embryology, School of Medicine, University of Athens, GR-11527 Athens, Greece.

Correspondence to: Thanos D. Halazonetis1,3 Email: thanos.halazonetis@unige.ch

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