Oncogenic HBV variants and integration are present in hepatic and lymphoid cells derived from chronic HBV patients.

Abstract:

:The hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), partly driven by viral integration and specific oncogenic HBV variants. However, the biological significance of HBV genomes within lymphoid cells (i.e., peripheral blood mononuclear cells, PBMCs) is unclear. Here, we collected available plasma, PBMC, liver, and tumor from 52 chronic HBV (CHB) carriers: 32 with HCC, 19 without HCC, and one with dendritic cell sarcoma, DCS. Using highly sensitive sequencing techniques, next generation sequencing, and AluPCR, we demonstrate that viral genomes (i.e., HBV DNA, RNA, and cccDNA), oncogenic variants, and HBV-host integration are often found in all sample types collected from 52 patients (including lymphoid cells and a DCS tumor). Viral integration was recurrently identified (n = 90 such hits) in genes associated with oncogenic consequences in lymphoid and liver cells. Further, HBV genomes increased in PBMCs derived from 7 additional (treated or untreated) CHB carriers after extracellular mitogen stimulation. Our study shows novel HBV molecular data and replication not only liver, but also within 63.8% of lymphoid cells analysed (including a representative lymphoid cell malignancy), that was enhanced in ex vivo stimulated PBMC.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Lau KC,Joshi SS,Gao S,Giles E,Swidinsky K,van Marle G,Bathe OF,Urbanski SJ,Terrault NA,Burak KW,Osiowy C,Coffin CS

doi

10.1016/j.canlet.2020.03.022

subject

Has Abstract

pub_date

2020-06-28 00:00:00

pages

39-47

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(20)30155-5

journal_volume

480

pub_type

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