Evidence map›Paper›PMID 28030832›Full record

ArticleOncotarget2017

Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis.

Aniruddha Chatterjee, Peter A Stockwell, Antonio Ahn, Euan J Rodger, Anna L Leichter, Michael R Eccles

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 2 pooled it
3.5field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Application of DNA Methylome Analysis to Patients with ME/CFS.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  9. Article
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  12. Exploring Potential Epigenetic Biomarkers for Colorectal Cancer Metastasis.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Article
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  20. Generating Sequencing-Based DNA Methylation Maps from Low DNA Input Samples.Methods in molecular biology (Clifton, N.J.) · 2022
    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

6 authors at 2 institutions in 1 country.

Aniruddha ChatterjeeDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Peter A StockwellDepartment of Biochemistry, University of Otago, Dunedin, New Zealand.
Antonio AhnDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Euan J RodgerDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Anna L LeichterDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Michael R EcclesDepartment of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Maurice Wilkins Centre · NZUniversity of Otago · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic alterations are increasingly implicated in metastasis, whereas very few genetic mutations have been identified as authentic drivers of cancer metastasis. Yet, to date, few studies have identified metastasis-related epigenetic drivers, in part because a framework for identifying driver epigenetic changes in metastasis has not been established. Using reduced representation bisulfite sequencing (RRBS), we mapped genome-wide DNA methylation patterns in three cutaneous primary and metastatic melanoma cell line pairs to identify metastasis-related epigenetic drivers. Globally, metastatic melanoma cell lines were hypomethylated compared to the matched primary melanoma cell lines. Using whole genome RRBS we identified 75 shared (10 hyper- and 65 hypomethylated) differentially methylated fragments (DMFs), which were associated with 68 genes showing significant methylation differences. One gene, Early B Cell Factor 3 (EBF3), exhibited promoter hypermethylation in metastatic cell lines, and was validated with bisulfite sequencing and in two publicly available independent melanoma cohorts (n = 40 and 458 melanomas, respectively). We found that hypermethylation of the EBF3 promoter was associated with increased EBF3 mRNA levels in metastatic melanomas and subsequent inhibition of DNA methylation reduced EBF3 expression. RNAi-mediated knockdown of EBF3 mRNA levels decreased proliferation, migration and invasion in primary and metastatic melanoma cell lines. Overall, we have identified numerous epigenetic changes characterising metastatic melanoma cell lines, including EBF3-induced aggressive phenotypic behaviour with elevated EBF3 expression in metastatic melanoma, suggesting that EBF3 promoter hypermethylation may be a candidate epigenetic driver of metastasis.

Indexed as

DNA MethylationCell Line, TumorCpG IslandsCutaneous Malignant MelanomaEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansMelanomaNeoplasm MetastasisPromoter Regions, GeneticSequence Analysis, DNASkin NeoplasmsTranscription FactorsUp-RegulationEBF3 protein, humanTranscription Factorsbisulfite sequencingcancer epigenomeDNA methylationmelanomametastasis

Identifiers

PMID28030832
PMCPMC5351615
OpenAlexW2567358926

What Socratic 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 Socratic graph.