Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations
| Autor: | Baback Gharizadeh, Han Chong Toh, Alexander Yf Chung, Mostafa Ronaghi, Pierce K. H. Chow, London L.P.J. Ooi, Caroline G.L. Lee, Soo Ting Toh, Yu Jin, Lizhen Liu, Farbod Babrzadeh, Jingbo Wang |
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| Rok vydání: | 2012 |
| Předmět: |
Hepatitis B virus
Cancer Research Carcinoma Hepatocellular Virus Integration Biology medicine.disease_cause Virus Hepatitis B virus PRE beta Cell Line Hepatitis B Chronic medicine Humans Viral Regulatory and Accessory Proteins Promoter Regions Genetic Telomerase Gene Base Sequence Chromosomes Human Pair 10 Liver Neoplasms Genetic Variation High-Throughput Nucleotide Sequencing Sequence Analysis DNA General Medicine Hepatitis B medicine.disease Virology Molecular biology digestive system diseases HBx Amino Acid Substitution Viral replication Hepatocellular carcinoma DNA Viral Trans-Activators |
| Zdroj: | Carcinogenesis. 34:787-798 |
| ISSN: | 1460-2180 0143-3334 |
| DOI: | 10.1093/carcin/bgs406 |
| Popis: | Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48 HCC patients using an oligo-bead-based strategy, pooled together and sequenced using the FLX-Genome-Sequencer. In the tumors, preferential integration of HBV into promoters of genes (P < 0.001) and significant enrichment of integration into chromosome 10 (P < 0.01) were observed. Integration into chromosome 10 was significantly associated with poorly differentiated tumors (P < 0.05). Notably, in the tumors, recurrent integration into the promoter of the human telomerase reverse transcriptase (TERT) gene was found to correlate with increased TERT expression. The preferred region within the HBV genome involved in integration and viral structural alteration is at the 3'-end of hepatitis B virus X protein (HBx), where viral replication/transcription initiates. Upon integration, the 3'-end of the HBx is often deleted. HBx-human chimeric transcripts, the most common type of chimeric transcripts, can be expressed as chimeric proteins. Sequence variation resulting in non-conservative amino acid substitutions are commonly observed in HBV genome. This study highlights HBV as highly mutable in HCC patients with preferential regions within the host and virus genome for HBV integration/structural alterations. |
| Databáze: | OpenAIRE |
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