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Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma

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 investigated the patterns of HBV integration and correlated them with TERT (telomerase reverse transcriptase) altera...

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Autores principales: Jang, Jeong-Won, Kim, Hye-Seon, Kim, Jin-Seoub, Lee, Soon-Kyu, Han, Ji-Won, Sung, Pil-Soo, Bae, Si-Hyun, Choi, Jong-Young, Yoon, Seung-Kew, Han, Dong-Jin, Kim, Tae-Min, Roberts, Lewis R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268258/
https://www.ncbi.nlm.nih.gov/pubmed/34209079
http://dx.doi.org/10.3390/ijms22137056
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author Jang, Jeong-Won
Kim, Hye-Seon
Kim, Jin-Seoub
Lee, Soon-Kyu
Han, Ji-Won
Sung, Pil-Soo
Bae, Si-Hyun
Choi, Jong-Young
Yoon, Seung-Kew
Han, Dong-Jin
Kim, Tae-Min
Roberts, Lewis R.
author_facet Jang, Jeong-Won
Kim, Hye-Seon
Kim, Jin-Seoub
Lee, Soon-Kyu
Han, Ji-Won
Sung, Pil-Soo
Bae, Si-Hyun
Choi, Jong-Young
Yoon, Seung-Kew
Han, Dong-Jin
Kim, Tae-Min
Roberts, Lewis R.
author_sort Jang, Jeong-Won
collection PubMed
description 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 investigated the patterns of HBV integration and correlated them with TERT (telomerase reverse transcriptase) 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 integration. 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-tumors. 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 recurrently affected by HBV integration included TERT and MLL4 for tumors and FN1 for non-tumors. 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 oncogenic regulatory function. The characteristic genomic features of HBV integration together with TERT alteration may dysregulate the affected gene function, thereby contributing to hepatocarcinogenesis.
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spelling pubmed-82682582021-07-10 Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma Jang, Jeong-Won Kim, Hye-Seon Kim, Jin-Seoub Lee, Soon-Kyu Han, Ji-Won Sung, Pil-Soo Bae, Si-Hyun Choi, Jong-Young Yoon, Seung-Kew Han, Dong-Jin Kim, Tae-Min Roberts, Lewis R. Int J Mol Sci Article 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 investigated the patterns of HBV integration and correlated them with TERT (telomerase reverse transcriptase) 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 integration. 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-tumors. 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 recurrently affected by HBV integration included TERT and MLL4 for tumors and FN1 for non-tumors. 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 oncogenic regulatory function. The characteristic genomic features of HBV integration together with TERT alteration may dysregulate the affected gene function, thereby contributing to hepatocarcinogenesis. MDPI 2021-06-30 /pmc/articles/PMC8268258/ /pubmed/34209079 http://dx.doi.org/10.3390/ijms22137056 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jang, Jeong-Won
Kim, Hye-Seon
Kim, Jin-Seoub
Lee, Soon-Kyu
Han, Ji-Won
Sung, Pil-Soo
Bae, Si-Hyun
Choi, Jong-Young
Yoon, Seung-Kew
Han, Dong-Jin
Kim, Tae-Min
Roberts, Lewis R.
Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
title Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
title_full Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
title_fullStr Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
title_full_unstemmed Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
title_short Distinct Patterns of HBV Integration and TERT Alterations between in Tumor and Non-Tumor Tissue in Patients with Hepatocellular Carcinoma
title_sort distinct patterns of hbv integration and tert alterations between in tumor and non-tumor tissue in patients with hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268258/
https://www.ncbi.nlm.nih.gov/pubmed/34209079
http://dx.doi.org/10.3390/ijms22137056
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