Evidence map›Paper›PMID 25619363›Full record

ArticleCancer medicine2015

Epigenetic changes in the CDKN2A locus are associated with differential expression of P16INK4A and P14ARF in HPV-positive oropharyngeal squamous cell carcinoma.

Nicolas F Schlecht, Miriam Ben-Dayan, Nicole Anayannis, Roberto A Lleras, Carlos Thomas, Yanhua Wang, Richard V Smith, Robert D Burk, Thomas M Harris, Geoffrey Childs and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Cancer Epigenomics and Beyond: Advancing the Precision Oncology Paradigm.Journal of immunotherapy and precision oncology · 2020
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Epigenetics of oropharyngeal squamous cell carcinoma: opportunities for novel chemotherapeutic targets.Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale · 2017
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Genomic insights into head and neck cancer.Cancers of the head & neck · 2016
    Article
  20. Article
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

13 authors at 3 institutions in 1 country.

Nicolas F SchlechtDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461; Department of Medicine (Oncology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461.
Miriam Ben-Dayan
Nicole Anayannis
Roberto A Lleras
Carlos Thomas
Yanhua Wang
Richard V Smith
Robert D Burk
Thomas M Harris
Geoffrey Childs
Thomas J Ow
Michael B Prystowsky
Thomas J Belbin
Albert Einstein College of Medicine · USMontefiore Medical Center · USPediatrics and Genetics · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Core-010UL1TR001073 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KELLER, MARLA J, SHAMOON, HARRY · 2013 to 2017
$21.3M
Identification and Classification of Epigenetic Changes in Head and Neck CancerR21CA131648 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI BELBIN, THOMAS J. · 2009 to 2010
$475k
Developing a HPV-mediated DNA methylation panel in HNSCCR21DE023941 · NIDCR · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BELBIN, THOMAS J., SCHLECHT, NICOLAS · 2013 to 2014
$459k
HPV Induced Pathogenesis in Head and Neck CancerR03CA115243 · NCI · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI SCHLECHT, NICOLAS · 2005 to 2006
$163k
NCATS NIH HHS UL1 TR001073NCI NIH HHS CA115243NCI NIH HHS CA131648NCI NIH HHS P30 CA013330NCI NIH HHS R03 CA115243NCI NIH HHS R21 CA131648NIDCR NIH HHS DE023941NIDCR NIH HHS R21 DE023941
6 · The paper itself

Abstract

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is recognized as a distinct disease entity associated with improved survival. DNA hypermethylation profiles differ significantly by HPV status suggesting that a specific subset of methylated CpG loci could give mechanistic insight into HPV-driven OPSCC. We analyzed genome-wide DNA methylation of primary tumor samples and adjacent normal mucosa from 46 OPSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M value). From these analyses, we identified a 22 CpG loci panel for HPV+ OPSCC that included four CDKN2A loci downstream of the p16(INK4A) and p14(ARF) transcription start sites. This panel was significantly associated with overall HPV detection (P < 0.05; ROC area under the curve = 0.96, 95% CI: 0.91-1.0) similar to the subset of four CDKN2A-specific CpG loci (0.90, 95% CI: 0.82-0.99) with equivalence to the full 22 CpG panel. DNA hypermethylation correlated with a significant increase in alternative open reading frame (ARF) expression in HPV+ OPSCC primary tumors, but not to the other transcript variant encoded by the CDKN2A locus. Overall, this study provides evidence of epigenetic changes to the downstream region of the CDKN2A locus in HPV+ oropharyngeal cancer that are associated with changes in expression of the coded protein products.

Indexed as

AdultAgedAged, 80 and overCarcinoma, Squamous CellCpG IslandsCyclin-Dependent Kinase Inhibitor p16DNA MethylationEpigenesis, GeneticFemaleHumansMaleMiddle AgedOropharyngeal NeoplasmsPapillomaviridaePapillomavirus InfectionsRNA, MessengerCyclin-Dependent Kinase Inhibitor p16RNA, MessengerTumor Suppressor Protein p14ARFCarcinomaHPVmethylationoropharynxsquamous

Identifiers

PMID25619363
PMCPMC4380960
OpenAlexW2021412272

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.