Complex clusters of rearrangements are a challenge in interpretation of cancer genomes. Some clusters of rearrangements demarcate clear amplifications of driver oncogenes but others are less well understood. The authors systematically investigate rearrangements that are densely clustered in individual tumours in a cohort of 560 breast cancers. Applying an agnostic approach, the authors identify 21 hotspots where clustered rearrangements recur across cancers. The work presents an overview of complex rearrangements in breast cancer, highlighting a potential new way for detecting drivers and revealing novel mechanistic insights into the formation of two common amplicons.

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