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Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma

BACKGROUND: Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis. However, the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated. AIM: To analyze the feature...

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Autores principales: Kojima, Ryuta, Nakamoto, Shingo, Kogure, Tadayoshi, Ma, Yaojia, Ogawa, Keita, Iwanaga, Terunao, Qiang, Na, Ao, Junjie, Nakagawa, Ryo, Muroyama, Ryosuke, Nakamura, Masato, Chiba, Tetsuhiro, Kato, Jun, Kato, Naoya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311580/
https://www.ncbi.nlm.nih.gov/pubmed/37396703
http://dx.doi.org/10.5501/wjv.v12.i3.209
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author Kojima, Ryuta
Nakamoto, Shingo
Kogure, Tadayoshi
Ma, Yaojia
Ogawa, Keita
Iwanaga, Terunao
Qiang, Na
Ao, Junjie
Nakagawa, Ryo
Muroyama, Ryosuke
Nakamura, Masato
Chiba, Tetsuhiro
Kato, Jun
Kato, Naoya
author_facet Kojima, Ryuta
Nakamoto, Shingo
Kogure, Tadayoshi
Ma, Yaojia
Ogawa, Keita
Iwanaga, Terunao
Qiang, Na
Ao, Junjie
Nakagawa, Ryo
Muroyama, Ryosuke
Nakamura, Masato
Chiba, Tetsuhiro
Kato, Jun
Kato, Naoya
author_sort Kojima, Ryuta
collection PubMed
description BACKGROUND: Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis. However, the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated. AIM: To analyze the features of HBV integration in HCC using a new reference database and integration detection method. METHODS: Published data, consisting of 426 Liver tumor samples and 426 paired adjacent non-tumor samples, were re-analyzed to identify the integration sites. Genome Reference Consortium Human Build 38 (GRCh38) and Telomere-to-Telomere Consortium CHM13 (T2T-CHM13 (v2.0)) were used as the human reference genomes. In contrast, human genome 19 (hg19) was used in the original study. In addition, GRIDSS VIRUSBreakend was used to detect HBV integration sites, whereas high-throughput viral integration detection (HIVID) was applied in the original study (HIVID-hg19). RESULTS: A total of 5361 integration sites were detected using T2T-CHM13. In the tumor samples, integration hotspots in the cancer driver genes, such as TERT and KMT2B, were consistent with those in the original study. GRIDSS VIRUSBreakend detected integrations in more samples than by HIVID-hg19. Enrichment of integration was observed at chromosome 11q13.3, including the CCND1 pro-moter, in tumor samples. Recurrent integration sites were observed in mitochondrial genes. CONCLUSION: GRIDSS VIRUSBreakend using T2T-CHM13 is accurate and sensitive in detecting HBV integration. Re-analysis provides new insights into the regions of HBV integration and their potential roles in HCC development.
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spelling pubmed-103115802023-07-01 Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma Kojima, Ryuta Nakamoto, Shingo Kogure, Tadayoshi Ma, Yaojia Ogawa, Keita Iwanaga, Terunao Qiang, Na Ao, Junjie Nakagawa, Ryo Muroyama, Ryosuke Nakamura, Masato Chiba, Tetsuhiro Kato, Jun Kato, Naoya World J Virol Basic Study BACKGROUND: Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis. However, the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated. AIM: To analyze the features of HBV integration in HCC using a new reference database and integration detection method. METHODS: Published data, consisting of 426 Liver tumor samples and 426 paired adjacent non-tumor samples, were re-analyzed to identify the integration sites. Genome Reference Consortium Human Build 38 (GRCh38) and Telomere-to-Telomere Consortium CHM13 (T2T-CHM13 (v2.0)) were used as the human reference genomes. In contrast, human genome 19 (hg19) was used in the original study. In addition, GRIDSS VIRUSBreakend was used to detect HBV integration sites, whereas high-throughput viral integration detection (HIVID) was applied in the original study (HIVID-hg19). RESULTS: A total of 5361 integration sites were detected using T2T-CHM13. In the tumor samples, integration hotspots in the cancer driver genes, such as TERT and KMT2B, were consistent with those in the original study. GRIDSS VIRUSBreakend detected integrations in more samples than by HIVID-hg19. Enrichment of integration was observed at chromosome 11q13.3, including the CCND1 pro-moter, in tumor samples. Recurrent integration sites were observed in mitochondrial genes. CONCLUSION: GRIDSS VIRUSBreakend using T2T-CHM13 is accurate and sensitive in detecting HBV integration. Re-analysis provides new insights into the regions of HBV integration and their potential roles in HCC development. Baishideng Publishing Group Inc 2023-06-25 2023-06-25 /pmc/articles/PMC10311580/ /pubmed/37396703 http://dx.doi.org/10.5501/wjv.v12.i3.209 Text en ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Kojima, Ryuta
Nakamoto, Shingo
Kogure, Tadayoshi
Ma, Yaojia
Ogawa, Keita
Iwanaga, Terunao
Qiang, Na
Ao, Junjie
Nakagawa, Ryo
Muroyama, Ryosuke
Nakamura, Masato
Chiba, Tetsuhiro
Kato, Jun
Kato, Naoya
Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
title Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
title_full Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
title_fullStr Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
title_full_unstemmed Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
title_short Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
title_sort re-analysis of hepatitis b virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311580/
https://www.ncbi.nlm.nih.gov/pubmed/37396703
http://dx.doi.org/10.5501/wjv.v12.i3.209
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