Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations

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Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations

Toh, Soo Ting (author)

Jin, Yu (author)

Liu, Lizhen (author)

Wang, Jingbo (author)

Babrzadeh, Farbod (author): Department of Biochemistry, Stanford Genome Technology Centre, Stanford University, Palo Alto, United States

Gharizadeh, Baback (author)

Ronaghi, Mostafa (author)

Toh, Han Chong (author)

Chow, Pierce Kah-Hoe (author)

Chung, Alexander Y-F. (author)

Ooi, London L-P-J. (author)

Lee, Caroline G-L. (author)

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(creator_code:org_t)

2012-12-30
2013
English.
In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 34:4, s. 787-798

Related links:: https://academic.oup...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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. HBxhuman 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.

Keyword

Amino Acid Substitution
Base Sequence
Carcinoma
Hepatocellular
Cell Line
Chromosomes
Human
Pair 10
DNA
Viral
Genetic Variation
Hepatitis B virus
Hepatitis B
Chronic
High-Throughput Nucleotide Sequencing
Humans
Liver Neoplasms
Promoter Regions
Genetic
Sequence Analysis
DNA
Telomerase
Trans-Activators
Virus Integration

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By the author/editor: Toh, Soo Ting; Jin, Yu; Liu, Lizhen; Wang, Jingbo; Babrzadeh, Farbo ...; Gharizadeh, Baba ...; show more...; Ronaghi, Mostafa; Toh, Han Chong; Chow, Pierce Kah ...; Chung, Alexander ...; Ooi, London L-P- ...; Lee, Caroline G- ...; show less...

Articles in the publication: Carcinogenesis

By the university: Royal Institute of Technology

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