{"id":2104,"date":"2026-06-26T11:37:38","date_gmt":"2026-06-26T02:37:38","guid":{"rendered":"https:\/\/lmi.jp\/articles\/?p=2104"},"modified":"2026-06-26T14:00:05","modified_gmt":"2026-06-26T05:00:05","slug":"unraveling-the-genomic-imprint-of-hbv-in-hepatocarcinogenesis","status":"publish","type":"post","link":"https:\/\/lmi.jp\/articles\/2026\/06\/26\/unraveling-the-genomic-imprint-of-hbv-in-hepatocarcinogenesis\/","title":{"rendered":"Unraveling the Genomic Imprint of HBV in Hepatocarcinogenesis"},"content":{"rendered":"\n


Hiroyasu Ito<\/strong><\/a>*<\/p>\n\n\n\n

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\u2003 Cite<\/span><\/span><\/i><\/i><\/span><\/summary>
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Ito H. Unraveling the Genomic Imprint of HBV in Hepatocarcinogenesis. Lab Med Int 2026; 5(1): 1-2: doi.org\/10.51041\/lmi.5.1_1<\/p>\n<\/div><\/details>\n<\/div>\n\n\n\n

Editorial
Lab Med Int 2026; 5(1): 1-2<\/p>\n\n\n\n

*Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University, 1-98 Dengakugakubo,
Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
E-mail: hiroyasu.ito”@”fujita-hu.ac.jp<\/p>\n\n\n\n

Download PDF<\/span><\/a><\/div>\n\n\n\n

See article volume 5<\/strong>(1<\/strong>): 3-19<\/strong><\/h2>\n\n\n\n

In this comprehensive review, Dr. Ogata presents a masterful synthesis of four decades of investigation into hepatitis B virus (HBV) integration and its role in hepatocellular carcinoma (HCC) development, a relationship first highlighted in early molecular studies. Advances in sequencing technologies\u2014from Southern blotting and Sanger sequencing to second- and third-generation sequencing\u2014have progressively refined our understanding of how HBV integrates into the human genome, particularly within repetitive genomic regions1)<\/strong><\/sup>. One of the most striking contributions detailed in this review is the discovery of HBV integration into centromeric alpha satellite DNA (\u03b1Sat), first reported by Dr. Ogata. This finding was later reinforced by computational approaches such as SurVirus2)<\/strong><\/sup> and long-read sequencing analyses3)<\/strong><\/sup>, which highlighted the centromere\u2014previously inaccessible due to its repetitive structure\u2014as a key locus where HBV-induced genomic instability may originate. The ability of HBV to integrate into \u03b1Sat suggests a direct mechanism between viral infection, disruption of centromere function, and aneuploidy, widely observed in HCC. This review also places HBV integration within broader cancer genomics efforts including TCGA and ICGC projects, which revealed that HBV frequently targets major cancer-related genes such as TERT<\/em>, KMT2B<\/em>, and CCNE1<\/em>1)4)<\/strong><\/sup>. Structural variations (SVs)\u2014including chromosomal amplifications, deletions, and translocations\u2014were shown to colocalize with HBV integration sites, with some SVs occurring decades before clinical HCC diagnosis4)<\/sup>. Long-read sequencing has further clarified these events, revealing that HBV can induce not only local but also distant genomic alterations, reshaping the tumor genome in profound ways3)<\/strong><\/sup>. Beyond genomic mapping, emerging proteogenomic insights show that although HBV-derived proteins may be detectable in HCC tissues, their expression does not strongly correlate with clinical outcomes5)<\/strong><\/sup>. These results suggest that while HBV protein expression may diminish over time, the genomic scars left behind\u2014such as HBV-driven SVs\u2014continue to influence tumor biology. The clinical implications of these findings are likely to be significant. Advances in liquid biopsy technology\u2014including methylated DNA assays and cfDNA-based repeat profiling\u2014have enabled promising new avenues for early HCC detection6)<\/strong><\/sup>. Meanwhile, therapeutic strategies targeting telomerase, particularly anti-TERT<\/em> approaches, have gained increasing traction due to the central role of TERT<\/em> activation in HBV-related HCC7)<\/strong><\/sup>. Taken together, this review illustrates a cohesive narrative: HBV integration is not a random genomic event but a structured, biologically significant process that interacts with centromeric biology, genomic stability, and cancer evolution. As long-read sequencing and telomere-to-telomere genome assemblies mature, repetitive DNA elements\u2014once viewed as \u201cgenetic dark matter\u201d\u2014are emerging as critical components in understanding HBV-mediated hepatocarcinogenesis8)<\/strong><\/sup>. This review not only synthesizes past knowledge but also illuminates future directions, urging deeper investigation into HBV integration within repetitive genomic elements and its implications for prevention, early detection, and personalized therapy of HBV-related HCC.<\/p>\n\n\n\n

References<\/strong><\/h2>\n\n\n\n
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  1. Totoki Y, Tatsuno K, Covington KR, et al. Trans-ancestry mutational landscape of hepatocellular carcinoma genomes. Nat Genet. 2014; 46(12): 1267-73.PubMed<\/a><\/span><\/li>\n\n\n\n
  2. Rajaby R, Zhou Y, Meng Y, et al. SurVirus: a repeat-aware virus integration caller. Nucleic Acids Res. 2021; 49(6): e33.PubMed<\/a><\/span><\/li>\n\n\n\n
  3. Zhuo Z, Rong W, Li H, et al. Long-read sequencing reveals the structural complexity of genomic integration of HBV DNA in hepatocellular carcinoma. NPJ Genom Med. 2021; 6(1): 84.PubMed<\/a><\/span><\/li>\n\n\n\n
  4. Qian Z, Liang J, Huang R, et al. HBV integrations reshaping genomic structures promote hepatocellular carcinoma. Gut. 2024; 73(7): 1169-82.PubMed<\/a><\/span><\/li>\n\n\n\n
  5. Gao Q, Zhu H, Doung L, et al. Integrated proteogenomic characterization of HBV-related hepatocellular carcinoma. Cell. 2019; 179(2): 561-77.PubMed<\/a><\/span><\/li>\n\n\n\n
  6. Sun J, Sun X, He W, et al. A liquid biopsy approach detects HCC and identifies GJA4 as a potential biomarker for HBV-HCC via plasma cfDNA methylome profiling. Clin Epigenetics. 2025; 17(1): 98.PubMed<\/a><\/span><\/li>\n\n\n\n
  7. Ningarhari M, Caruso S, Hirsch TZ, et al. Telomere length is key to hepatocellular carcinoma diversity and telomerase addiction is an actionable therapeutic target. J Hepatol. 2021; 74(5): 1155-66.PubMed<\/a><\/span><\/li>\n\n\n\n
  8. Altemose N, Logsdon GA, Bzikadze AV, et al. Complete genomic and epigenetic maps of human centromeres. Science. 2022; 376(6588): eabl4178.PubMed<\/a><\/span><\/li>\n<\/ol>\n\n\n\n

    This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0)<\/p>\n","protected":false},"excerpt":{"rendered":"

    Hiroyasu Ito* EditorialLab Med Int 2026; 5(1): 1-2 *Department of Joint Research Laboratory of Clinical Medici […]<\/p>\n","protected":false},"author":1,"featured_media":2107,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"swell_btn_cv_data":"","footnotes":""},"categories":[180,179],"tags":[183],"class_list":["post-2104","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-editorial-lab-med-int-2026-51","category-lab-med-int-2026-51","tag-lab-med-int-2026-51"],"_links":{"self":[{"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/posts\/2104","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/comments?post=2104"}],"version-history":[{"count":5,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/posts\/2104\/revisions"}],"predecessor-version":[{"id":2115,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/posts\/2104\/revisions\/2115"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/media\/2107"}],"wp:attachment":[{"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/media?parent=2104"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/categories?post=2104"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lmi.jp\/articles\/wp-json\/wp\/v2\/tags?post=2104"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}