Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Noninvasive chimeric DNA profiling identifies tumor-originated HBV integrants contributing to viral antigen expression in liver cancer.
Hepatol. Int. 14, 326–337 (2020)
Background Host genome integration of HBV sequence is considered to be significant in HBV antigen expression and the development of hepatocellular carcinoma (HCC). Method We developed a probe-based capture strategy to enrich integrated HBV DNA for deep-sequencing analysis of integration sites in paired patient samples derived from tumor, liver tissue adjacent to tumor, saliva and plasma, as a platform for exploring the correlation, significance and utility of detecting integrations in these sample types. Results Most significantly, alpha fetoprotein levels significantly correlated to the amounts of integrations detected in tumor. Viral-host chimeric DNA fragments were successfully detected at high sequencing coverage in plasma rather than saliva samples from HCC patients, and each fragment of this type was only seen once in plasma from chronic hepatitis B patients. Almost all plasma chimeric fragments were derived from integrations in tumor rather than in adjacent liver tissues. Over 50% of them may produce viral-host chimeric transcripts according to deep RNA sequencing in paired tissue samples. Particularly, in patients with low HBV DNA level (< 250 UI/ml), the seemingly normal HBsAg titers may be explained by larger amounts of integrations detected. Meanwhile, we developed a strategy to predict integrants by pairing breakpoints for each integration event. Among four resolved viral patterns, the majority of Pattern I events (81.2%) retained the complete opening reading frame for HBV surface proteins. Conclusion We achieve the efficient enrichment of plasma cell-free chimeric DNA from integration site, and demonstrate that chimeric DNA profiling in plasma is a promising noninvasive approach to monitor HBV integration in liver cancer development and to determine the ability of integrated sequences to express viral proteins that can be targeted, e.g. by immunotherapies.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Circulating Cell-free Dna ; Liquid Biopsy ; Dna Capture ; Viral Integration ; Repeat Elements ; Hepatocellular Carcinoma ; Alpha Fetoprotein ; Hbsag ; Neoantigen ; Immune Therapy ; Saliva; B Virus-dna
ISSN (print) / ISBN
1936-0533
e-ISSN
1936-0541
Zeitschrift
Hepatology international
Quellenangaben
Band: 14,
Seiten: 326–337
Verlag
Springer
Verlagsort
New York
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Virology (VIRO)