Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

Vassilis G. Gorgoulis, Leandros-Vassilios F. Vassiliou, Panagiotis Karakaidos, Panayotis Zacharatos, Athanassios Kotsinas, Triantafillos Liloglou, Monica Venere, Richard A. DiTullio, Nikolaos G. Kastrinakis, Brynn Levy, Dimitris Kletsas, Akihiro Yoneta, Meenhard Herlyn, Christos Kittas and Thanos D. Halazonetis ()
Additional contact information
Vassilis G. Gorgoulis: School of Medicine, University of Athens
Leandros-Vassilios F. Vassiliou: School of Medicine, University of Athens
Panagiotis Karakaidos: School of Medicine, University of Athens
Panayotis Zacharatos: School of Medicine, University of Athens
Athanassios Kotsinas: School of Medicine, University of Athens
Triantafillos Liloglou: Cancer Research Center, University of Liverpool
Monica Venere: The Wistar Institute
Richard A. DiTullio: The Wistar Institute
Nikolaos G. Kastrinakis: School of Medicine, University of Athens
Brynn Levy: Mount Sinai School of Medicine
Dimitris Kletsas: National Centre of Scientific Research ‘Demokritos’
Akihiro Yoneta: The Wistar Institute
Meenhard Herlyn: The Wistar Institute
Christos Kittas: School of Medicine, University of Athens
Thanos D. Halazonetis: The Wistar Institute

Nature, 2005, vol. 434, issue 7035, 907-913

Abstract: Cancer checkpoint Two groups this week report findings that could have a big impact on our view of cancer development. Both looked at tumours (bladder, breast and colorectal, and in lung and skin) in various stages of progression for signs of a DNA damage response. And both find that early stages of cancer development are associated with an active DNA damage response and p53-dependent cell death. This suggests that the induction of a DNA damage response by oncogenic events is a potent tumour suppression mechanism, and explains the selective pressure for p53 mutations in precancerous lesions. Importantly, activation of the DNA damage checkpoint occurs before chromosome instability and malignancy. On the cover, 53BP1 foci in lung hyperplasia (green indicates DNA damage checkpoint activation).

Date: 2005
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DOI: 10.1038/nature03485

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