The myriad changes that occur during the malignant progression of cancer cells present challenges to both clinicians and basic scientists. Two new studies in Nature underscore the central role of genome instability in tumor biology (Edwards et al., 2008; Sakai et al., 2008). These reports describe secondary changes in the BRCA2 locus that restore the wild-type reading frame and contribute to the development of resistance to chemotherapeutic agents.
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