Distinct patterns of hbv integration and tert alterations between in tumor and non-tumor tissue in patients with hepatocellular carcinoma

Jeong Won Jang, Hye Seon Kim, Jin Seoub Kim, Soon Kyu Lee, Ji Won Han, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Dong Jin Han, Tae Min Kim, Lewis R. Roberts

Research output: Contribution to journalArticlepeer-review


Although hepatitis B virus (HBV) integration into the cellular genome is well known in HCC (hepatocellular carcinoma) patients, its biological role still remains uncertain. This study in-vestigated the patterns of HBV integration and correlated them with TERT (telomerase reverse tran-scriptase) alterations in paired tumor and non-tumor tissues. Compared to those in non-tumors, tumoral integrations occurred less frequently but with higher read counts and were more preferentially observed in genic regions with significant enrichment of integration into promoters. In HBV-related tumors, TERT promoter was identified as the most frequent site (38.5% (10/26)) of HBV in-tegration. TERT promoter mutation was observed only in tumors (24.2% (8/33)), but not in non-tumors. Only 3.00% (34/1133) of HBV integration sites were shared between tumors and non-tu-mors. Within the HBV genome, HBV breakpoints were distributed preferentially in the 3’ end of HBx, with more tumoral integrations detected in the preS/S region. The major genes that were re-currently affected by HBV integration included TERT and MLL4 for tumors and FN1 for non-tu-mors. Functional enrichment analysis of tumoral genes with integrations showed enrichment of cancer-associated genes. The patterns and functions of HBV integration are distinct between tumors and non-tumors. Tumoral integration is often enriched into both human-virus regions with onco-genic regulatory function. The characteristic genomic features of HBV integration together with TERT alteration may dysregulate the affected gene function, thereby contributing to hepatocarcin-ogenesis.

Original languageEnglish (US)
Article number7056
JournalInternational journal of molecular sciences
Issue number13
StatePublished - Jul 1 2021


  • Hepatitis B virus
  • Liver cancer
  • Point mutation
  • Telomerase
  • Virus integration

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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