Fig. 5: HBV-mediated rearrangements are early clonal events in HCC evolution.

a In SA269680, an HCC with a whole-genome duplication, HBV insertions are shown in the context of point mutation burden for that sample. Coloured dots above chromosomes represent point mutations with different timing: early clonal (before the whole-genome duplication; green), late clonal (after the whole-genome duplication; purple), clonal (blue), subclonal (red). We identified nine HBV single clusters (black dots with red arrows), all but one catalogued as early clonal events. Five of these early HBV insertions (marked with red asterisks) are associated with megabase-size telomeric deletions (see copy number plots in Supplementary Fig. 3). The same sample bears two additional early clonal HBV canonical insertions (black dots with black arrows). Grey blocks below chromosomes represent the copy number profile. MCN stands for Minor Copy Number. b Real-time timing estimation of HBV insertions along patients’ lifetime in samples with whole-genome duplication events. The X axis shows the time interval when – before (green) and after (purple) – the somatic HBV insertions took place relative to the WGD event; thickness and strength of the green and purple bars correlates with the number of events. Black arrows represent when a WGD event took place, and numbers above arrows show the time – in years – before HCC diagnosis when the WGD event has occurred. Numbers within green and purple timelines represent the number of insertion events. Numbers at the end of the timeline represent the age of the patient at diagnosis. c Copy number plot showing a single cluster that supports an HBV insertion event (red triangle) associated with a 7 Mb telomeric deletion on chromosome 10 in SA501645 that, according to Fig. 4b, occurred at least 20.96 years before HCC diagnosis. The gold line represents total chromosome CN, and the grey line is the minor chromosome CN.