Evidence map›Paper›PMID 25798207›Full record

ArticleClinical epigenetics2015

Inter-locus as well as intra-locus heterogeneity in LINE-1 promoter methylation in common human cancers suggests selective demethylation pressure at specific CpGs.

Nicole Nüsgen, Wolfgang Goering, Albertas Dauksa, Arijit Biswas, Muhammad Ahmer Jamil, Ioanna Dimitriou, Amit Sharma, Heike Singer, Rolf Fimmers, Holger Fröhlich and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  4. Many Different LINE-1 Retroelements Are Activated in Bladder Cancer.International journal of molecular sciences · 2020
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  18. Epigenetic basis of cancer health disparities: Looking beyond genetic differences.Biochimica et biophysica acta. Reviews on cancer · 2017
    Review
  19. Article
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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

14 authors at 4 institutions in 2 countries.

Nicole NüsgenInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
Wolfgang GoeringDepartment of Urology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
Albertas DauksaInstitute for Digestive Research, Lithuanian University of Health Sciences, Eiveniu g. 2, Kaunas, 50009 Lithuania.
Arijit BiswasInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
Muhammad Ahmer JamilInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany ; Bonn-Aachen International Center for IT (B-IT) Algorithmic Bioinformatics, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany.
Ioanna DimitriouInstitute of Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
Amit SharmaInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
Heike SingerInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
Rolf FimmersInstitute of Medical Biometry, Informatics and Epidemiology (IMBIE), University of Bonn, Sigmund-Freud-Straße 25, D-53127 Bonn, Germany.
Holger FröhlichBonn-Aachen International Center for IT (B-IT) Algorithmic Bioinformatics, University of Bonn, Dahlmannstr. 2, 53113 Bonn, Germany.
Johannes OldenburgInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
Antanas GulbinasInstitute for Digestive Research, Lithuanian University of Health Sciences, Eiveniu g. 2, Kaunas, 50009 Lithuania.
Wolfgang A SchulzDepartment of Urology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
Osman El-MaarriInstitute of Experimental Hematology and Transfusion Medicine, University of Bonn, Sigmund-Freud Str. 25, 53127 Bonn, Germany.
University of Bonn · DEHeinrich Heine University Düsseldorf · DELithuanian University of Health Sciences · LTInstitut für Medizinische Biometrie, Informatik und Epidemiologie · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypomethylation of long interspersed element (LINE)-1 has been observed in tumorigenesis when using degenerate assays, which provide an average across all repeats. However, it is unknown whether individual LINE-1 loci or different CpGs within one specific LINE-1 promoter are equally affected by methylation changes. Conceivably, studying methylation changes at specific LINE-1 may be more informative than global assays for cancer diagnostics. Therefore, with the aim of mapping methylation at individual LINE-1 loci at single-CpG resolution and exploring the diagnostic potential of individual LINE-1 locus methylation, we analyzed methylation at 11 loci by pyrosequencing, next-generation bisulfite sequencing as well as global LINE-1 methylation in bladder, colon, pancreas, prostate, and stomach cancers compared to paired normal tissues and in blood samples from some of the patients compared to healthy donors.

resultsMost (72/80) tumor samples harbored significant methylation changes at at least one locus. Notably, our data revealed not only the expected hypomethylation but also hypermethylation at some loci. Specific CpGs within the LINE-1 consensus sequence appeared preferentially hypomethylated suggesting that these could act as seeds for hypomethylation. In silico analysis revealed that these CpG sites more likely faced the histones in the nucleosome. Multivariate logistic regression analysis did not reveal a significant clinical advantage of locus-specific methylation markers over global methylation markers in distinguishing tumors from normal tissues.

conclusionsMethylation changes at individual LINE-1 loci are heterogeneous, whereas specific CpGs within the consensus sequence appear to be more prone to hypomethylation. With a broader selection of loci, locus-specific LINE-1 methylation could become a tool for tumor detection.

Indexed as

Bisulfite sequencingCancerCancer classificationDNA methylationGlobal methylationL1 lociLINE-1Methylation patternsPyrosequencing

Identifiers

PMID25798207
PMCPMC4367886
OpenAlexW2120956614

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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.