HBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan

2003 ◽  
Vol 71 (4) ◽  
pp. 492-498 ◽  
Author(s):  
Akihiro Tamori ◽  
Shuhei Nishiguchi ◽  
Shoji Kubo ◽  
Takashi Narimatsu ◽  
Daiki Habu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hbv Dna ◽  
Transcript Expression ◽  
Dna Integration ◽  
Hbv Dna Integration

scholarly journals Molecular Characterization of HBV DNA Integration in Patients with Hepatitis and Hepatocellular Carcinoma

2018 ◽  
Vol 9 (18) ◽  
pp. 3225-3235 ◽  
Author(s):  
Liu Yang ◽  
Song Ye ◽  
Xinyi Zhao ◽  
Liyan Ji ◽  
Yinxin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Characterization ◽  
Hbv Dna ◽  
Dna Integration ◽  
Hbv Dna Integration

scholarly journals Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma

2015 ◽  
Vol 35 (10) ◽  
pp. 2311-2317 ◽  
Author(s):  
Carlo Saitta ◽  
Gianluca Tripodi ◽  
Adalberto Barbera ◽  
Antonio Bertuccio ◽  
Antonina Smedile ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Occult Hbv Infection ◽  
Dna Integration ◽  
Occult Hbv ◽  
B Virus ◽  
Hbv Dna Integration

scholarly journals Long-read sequencing reveals the structural complexity of genomic integration of HBV DNA in hepatocellular carcinoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhongling Zhuo ◽  
Weiqi Rong ◽  
Hexin Li ◽  
Ying Li ◽  
Xuanmei Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Genome ◽  
Hbv Dna ◽  
Host Cells ◽  
Dna Integration ◽  
Genomic Integration ◽  
Integration Pattern ◽  
Intergenic Sequences ◽  
Long Read ◽  
Hbv Dna Integration

AbstractThe integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.

scholarly journals Whole exome HBV DNA integration is independent of the intrahepatic HBV reservoir in HBeAg-negative chronic hepatitis B

Gut ◽  
2020 ◽  
pp. gutjnl-2020-323300
Author(s):  
Valentina Svicher ◽  
Romina Salpini ◽  
Lorenzo Piermatteo ◽  
Luca Carioti ◽  
Arianna Battisti ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hbv Dna ◽  
Dna Integration ◽  
Whole Exome ◽  
Number Of Patients ◽  
Hbv Dna Integration ◽  
Intrahepatic Hbv ◽  
Negative Chronic Hepatitis

ObjectiveThe involvement of HBV DNA integration in promoting hepatocarcinogenesis and the extent to which the intrahepatic HBV reservoir modulates liver disease progression remains poorly understood. We examined the intrahepatic HBV reservoir, the occurrence of HBV DNA integration and its impact on the hepatocyte transcriptome in hepatitis B ‘e’ antigen (HBeAg)-negative chronic hepatitis B (CHB).DesignLiver tissue from 84 HBeAg-negative patients with CHB with low (n=12), moderate (n=25) and high (n=47) serum HBV DNA was analysed. Covalently closed circular DNA (cccDNA), pregenomic RNA (pgRNA) were evaluated by quantitative PCR, whole exome and transcriptome sequencing was performed by Illumina, and the burden of HBV DNA integrations was evaluated by digital droplet PCR.ResultsPatients with low and moderate serum HBV DNA displayed comparable intrahepatic cccDNA and pgRNA, significantly lower than in patients with high HBV DNA, while hepatitis B core-related antigen correlated strongly with the intrahepatic HBV reservoir, reflecting cccDNA quantity. Whole exome integration was detected in a significant number of patients (55.6%, 14.3% and 25% in high, moderate and low viraemic patients, respectively), at a frequency ranging from 0.5 to 157 integrations/1000 hepatocytes. Hepatitis B surface antigen >5000 IU/mL predicted integration within the exome and these integrations localised in genes involved in hepatocarcinogenesis, regulation of lipid/drug metabolism and antiviral/inflammatory responses. Transcript levels of specific genes, including the proto-oncogene hRAS, were higher in patients with HBV DNA integration, supporting an underlying oncogenic risk in patients with low-level to moderate-level viraemia.ConclusionsHBV DNA integration occurs across all HBeAg-negative patients with CHB, including those with a limited HBV reservoir; localising in genes involved in carcinogenesis and altering the hepatocyte transcriptome.

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