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Recent progress indicates that some of the most common fragile sites in human neoplasm assume non\u2010B DNA structures, namely deviations from the Watson\u2013Crick helix. Because of the single strandedness within these non\u2010B structures, they are vulnerable to structure\u2010specific nucleases. Here we summarize these findings and integrate them with other recent data for non\u2010B structures at sites of consistent constitutional chromosomal translocations. 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