Evidence map›Paper›PMID 33374558›Full record

ArticleCancers2020

Global Genome Demethylation Causes Transcription-Associated DNA Double Strand Breaks in HPV-Associated Head and Neck Cancer Cells.

Michael Hajek, Asel Biktasova, Andrew Sewell, Cyril Gary, Paul Cantalupo, Karen S Anderson, Wendell G Yarbrough, Natalia Issaeva

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
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

7 citing papers in PubMed, 9 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

8 authors at 3 institutions in 1 country.

Michael HajekDepartment of Surgery, Otolaryngology, Yale University, New Haven, CT 06519-1369, USA.
Asel BiktasovaDepartment of Surgery, Otolaryngology, Yale University, New Haven, CT 06519-1369, USA.ORCID 0000-0003-0855-6444
Andrew SewellDepartment of Surgery, Otolaryngology, Yale University, New Haven, CT 06519-1369, USA.
Cyril GaryDepartment of Surgery, Otolaryngology, Yale University, New Haven, CT 06519-1369, USA.
Paul CantalupoDepartment of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Karen S AndersonDepartment of Pharmacology, Yale University School of Medicine, New Haven, CT 06519-1369, USA.
Wendell G YarbroughDepartment of Otolaryngology/Head and Neck Surgery, The University of North Carolina, Chapel Hill, NC 27599-7070, USA.
Natalia IssaevaDepartment of Otolaryngology/Head and Neck Surgery, The University of North Carolina, Chapel Hill, NC 27599-7070, USA.ORCID 0000-0003-3966-8481
Yale University · USUniversity of North Carolina at Chapel Hill · USUniversity of Pittsburgh · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Exploring mechanisms of therapeutic demethylation effects in HPV-associated head and neck cancerR01DE027942 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ANDERSON, KAREN S., ISSAEVA, NATALIA · 2019 to 2023
$2.1M
Yale University Clinical and Translational Science Award ProgramTL1TR000141 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$720k
NCATS NIH HHS UL1 TR001863NIDCR NIH HHS R01 DE027942NIH HHS 1R01DE027942-01A1NIH HHS TL1TR000141
6 · The paper itself

Abstract

High levels of DNA methylation at CpG loci are associated with transcriptional repression of tumor suppressor genes and dysregulation of DNA repair genes. Human papilloma virus (HPV)-associated head and neck squamous cell carcinomas (HNSCC) have high levels of DNA methylation and methylation has been associated with dampening of an innate immune response in virally infected cells. We have been exploring demethylation as a potential treatment in HPV+ HNSCC and recently reported results of a window clinical trial showing that HNSCCs are particularly sensitive to demethylating agent 5-azacytidine (5-aza). Mechanistically, sensitivity is partially due to downregulation of HPV genes expression and restoration of tumor suppressors p53 and Rb. Here, for the first time, we show that 5-azaC treatment of HPV+ HNSCC induces replication and transcription-associated DNA double strand breaks (DSBs) that occur preferentially at demethylated genomic DNA. Blocking replication or transcription prevented formation of DNA DSBs and reduced sensitivity of HPV-positive head and neck cancer cells to 5-azaC, demonstrating that both replication and active transcription are required for formation of DSBs associated with 5-azaC.

Indexed as

demethylationDNA double strand breakshead and neck cancerHPVreplicationtranscription

Identifiers

PMID33374558
PMCPMC7793113
OpenAlexW3115925700

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.