Evidence map›Paper›PMID 25653310›Full record

ArticleGenome research2015

DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences.

Yoshiyuki Watanabe, Hiroyuki Yamamoto, Ritsuko Oikawa, Minoru Toyota, Masakazu Yamamoto, Norihiro Kokudo, Shinji Tanaka, Shigeki Arii, Hiroshi Yotsuyanagi, Kazuhiko Koike and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Yoshiyuki WatanabeDivision of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan; Internal Medicine, Kawasaki Rinko General Hospital, Kawasaki 210-0806, Japan;
Hiroyuki YamamotoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan;
Ritsuko OikawaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan;
Minoru ToyotaDepartment of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan;
Masakazu YamamotoDepartment of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo 162-8666, Japan;
Norihiro KokudoHepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo 113-8655, Japan;
Shinji TanakaDepartment of Hepatobiliary Pancreatic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo 113-0034, Japan;
Shigeki AriiDepartment of Hepatobiliary Pancreatic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo 113-0034, Japan;
Hiroshi YotsuyanagiDepartment of Infectious Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan;
Kazuhiko KoikeDepartment of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Fumio ItohDivision of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan;
St. Marianna University School of Medicine · JPThe University of Tokyo · JPTokyo Medical and Dental University · JPSapporo Medical University · JPTokyo Women's Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis.

Indexed as

DNA MethylationGenome, HumanVirus IntegrationAllelesAlu ElementsCarcinoma, HepatocellularCell Line, TumorCpG IslandsDNA, ViralEpigenesis, GeneticGenetic LociGenome, ViralHepatitis B virusHigh-Throughput Nucleotide SequencingHumansIn Situ Hybridization, FluorescenceDNA, Viral

Identifiers

PMID25653310
PMCPMC4352876
OpenAlexW1977484499

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.