Fig. 7: HBV-mediated translocations lead to recurrent loss of tumour suppressor gene ARID1A.

a In HCC tumour SA501481, the Illumina paired-end data (short-reads in red) shows two clusters, one on chromosome 1 and another on chromosome 9, which point to both extremes of an HBV insertion. The copy number (CN) plot at the top shows the total (gold line) and minor (grey line) chromosomes’ copy number profiles. The CN plot reveals two telomeric deletions associated with HBV events, one that removes 57.2 Mb on 1p, including one copy of the ARID1A tumour suppressor gene, and a second deletion that removes 21.2 Mb on 9p. Note the CN plot from chromosome 1 is flipped for illustrative purposes. The long-read plot shows a 2688 bp HBV insertion that bridges an interchromosomal rearrangement between chromosomes 1p and 9p. The configuration of the rearrangement predicts the formation of a dicentric chromosome (Fig. 3b). b A similar scenario, in tumour SA501424, where an HBV DNA insertion induces an interchromosomal translocation between chromosomes 1 and 11. The Illumina paired-end data (short-reads in red) shows two single clusters, one on chromosome 1 and another on chromosome 11, which point to both extremes of an HBV insertion. The CN plot at the top reveals a 31.5 Mb telomeric deletion on 1p associated with the HBV insertion event (note that the CN plot from chromosome 1 is flipped for illustrative purposes). Here, the associated telomeric deletion on chromosome 1 removes one copy of tumour suppressor gene ARID1A. The long-read alignment plot demonstrates an interchromosomal rearrangement between chromosomes 1 and 11 mediated by an HBV insertion. The long-reads used to construct the long-read plots are annotated in Supplementary Table 1.