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Emerging epidemiological evidence suggests a link between hepatitis B virus (HBV) infection and PDAC. However, the underlying mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>High\u2010throughput sequencing\u2010based approach was employed to identify HBV integrations in tumour and para\u2010tumour tissues of PDAC. The biological functions of KMT2B were evaluated in PDAC cell lines as well as in subcutaneous and orthotopic mouse models of PDAC. Chromatin immunoprecipitation sequencing and RNA sequencing were used to identify the pathway involved in PDAC development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HBV integration was detected in approximately one\u2010third of HBV DNA\u2010positive PDAC and adjacent para\u2010tumour tissues. A total of 425 viral\u2012host junctions were identified, with the majority located in intergenic regions (51.29%), followed by introns (43.29%) and exons (2.35%) of the human genome. Lysine methyltransferase 2B (\n                      <jats:italic>KMT2B<\/jats:italic>\n                      , also known as\n                      <jats:italic>MLL4<\/jats:italic>\n                      ), a gene frequently targeted by HBV integration in hepatocellular carcinoma, was also found to be interrupted by HBV in PDAC. KMT2B was significantly upregulated in PDAC and promoted malignant behaviours both in vitro and in vivo. Mechanistically, KMT2B exerts its oncogenic effects by regulating the downstream target gene\n                      <jats:italic>FYN<\/jats:italic>\n                      through histone H3K4 trimethylation, leading to the activation of the PI3K\/Akt signalling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      HBV integration is a common event in HBV\u2010related PDAC and\n                      <jats:italic>KMT2B<\/jats:italic>\n                      has been identified as a novel PDAC\u2010related gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Hepatitis B virus (HBV) integrates in both tumour and adjacent para\u2010tumour tissues of pancreatic ductal adenocarcinoma (PDAC).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>KMT2B<\/jats:italic>\n                            , a target gene of HBV integration, promotes PDAC proliferation and metastasis in vivo and in vitro experiments.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            KMT2B exerts its oncogenic effects by regulating the downstream target gene\n                            <jats:italic>FYN<\/jats:italic>\n                            via histone H3K4 trimethylation, activating the PI3K\/Akt signalling pathway.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      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