|Title:||Re-evaluation of the Carcinogenic Significance of Hepatitis B Virus Integration in Hepatocarcinogenesis||Authors:||Jiang S.
|Issue Date:||2012||Publisher:||Public Library of Science||Journal Volume:||7||Journal Issue:||9||Start page/Pages:||e40363||Source:||PLoS ONE||Abstract:||
To examine the role of hepatitis B virus (HBV) integration in hepatocarcinogenesis, a systematic comparative study of both tumor and their corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across all human chromosomes at random, no difference between tumor and non-tumor tissue was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in close proximity to cancer related genes such as hTERT were found in this study, however overall they were rare events. No direct correlation between chromosome aberrations and the number of HBV integration events was found using a sensitive array-based comparative genomic hybridization (aCGH) assay. However, a positive correlation was observed between the status of several tumor suppressor genes (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r = 0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts were in the preC/C region and 57% were in the HBV X gene. Strikingly, approximately 24% of the integrations examined had a breakpoint in a short 15 nt viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene insertions were C-terminal truncated, losing their growth-suppressive domain. However, the same pattern of X gene C-terminal truncation was found in both tumor and non-tumor derived samples. Furthermore, the integrated viral sequences in both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A mutations. The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis. ? 2012 Jiang et al.
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0040363||metadata.dc.subject.other:||hepatitis B virus X protein; protein p53; adult; aged; article; carboxy terminal sequence; CDNK2A gene; chromosome aberration; chromosome number; comparative genomic hybridization; controlled study; female; gene insertion; Hepatitis B virus; human; human chromosome; human tissue; liver carcinogenesis; male; nonhuman; nucleotide sequence; oncogene; polymerase chain reaction; RB1 gene; TP73 gene; tumor suppressor gene; virus DNA cell DNA interaction; virus genome; Hepatitis B virus
|Appears in Collections:||臨床醫學研究所|
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