Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/37783
Title: CHARACTERIZATION OF HEPATITIS B VIRUS (HBV) IN HEPATOCELLULAR CARCINOMA (HCC) PATIENTS
Authors: TOH SOO TING
Keywords: Liver Cancer, HBV Integration, Structural Alterations, Chimeric Transcripts, Next Generation Sequencing
Issue Date: 5-Mar-2013
Source: TOH SOO TING (2013-03-05). CHARACTERIZATION OF HEPATITIS B VIRUS (HBV) IN HEPATOCELLULAR CARCINOMA (HCC) PATIENTS. ScholarBank@NUS Repository.
Abstract: 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. Here, 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) was 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 as well as viral structural alteration is at the 3¿-end of 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.
URI: http://scholarbank.nus.edu.sg/handle/10635/37783
Appears in Collections:Ph.D Theses (Open)

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