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This year marks the 15th anniversary of the first whole cancer genome to be sequenced in acute myeloid leukemia cells (Nature. 2008 Nov 6; 456(7218): 66–72). The field has moved on enormously over a short period of time; tumor whole-genome sequencing is now commonplace and fast becoming standard of care. Vast amounts of sequence data are being generated and new ways to analyze these data are regularly put forward – meaning that multiple different approaches can now be used, depending on the questions being addressed. Tumor sequencing is arguably the biggest driving factor behind the development of precision oncology with personalized treatments tailored for each individual. In this collection, we aim to highlight some of the recent advances and address some of the key questions in the field.