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

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).