Evidence map›Paper›PMID 21871071›Full record

ArticleBMC cancer2011

EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation.

Lisa C Neumann, Andreas Weinhäusel, Stefanie Thomas, Bernhard Horsthemke, Dietmar R Lohmann, Michael Zeschnigk

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Uveal melanoma: progress in molecular biology and therapeutics.Therapeutic advances in medical oncology · 2020
    Review
  6. BAP1 Loss Is Associated with DNA Methylomic Repatterning in Highly Aggressive Class 2 Uveal Melanomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Article
  7. Primary and Metastatic Melanoma With NTRK Fusions.The American journal of surgical pathology · 2018
    Article
  8. DNA Methylation and Uveal Melanoma.Chinese medical journal · 2018
    Review
  9. Review
  10. Epigenetics and Common Ophthalmic Diseases.The Yale journal of biology and medicine · 2016
    Review
  11. Article
  12. Article
  13. Review
  14. Decreased expression of EFS is correlated with the advanced prostate cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  15. Article
  16. Molecular pathology of uveal melanoma.Eye (London, England) · 2013
    Review
  17. Article
  18. Review
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 3 institutions in 2 countries.

Lisa C NeumannInstitut für Humangenetik, Universitätsklinikum Essen, Hufelandstr, 55, 45157 Essen, Germany.
Andreas Weinhäusel
Stefanie Thomas
Bernhard Horsthemke
Dietmar R Lohmann
Michael Zeschnigk
Essen University Hospital · DEInstitut für Medizinische Informatik, Biometrie und Epidemiologie · DESeibersdorf Laboratories (Austria) · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated EFS promoter region CpG island in tumor classification and metastatic progression.

methodsEFS methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients.

resultsAnalysis of 16 UM showed full methylation of the EFS CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with EFS methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with EFS methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of EFS mRNA expression with EFS methylation in UM. We further found that EFS methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. EFS methylation always affects both alleles in normal and tumor samples.

conclusionsBiallelic EFS methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The EFS methylation of a UM may depend on which type of precursor cell the tumor originated from.

Indexed as

DNA MethylationAdaptor Proteins, Signal TransducingAdultAgedBase SequenceCells, CulturedCpG IslandsFemaleHumansMaleMelanomaMiddle AgedMolecular Sequence DataNeoplasm MetastasisOrgan SpecificityPhosphoproteinsAdaptor Proteins, Signal TransducingEFS protein, humanPhosphoproteins

Identifiers

PMID21871071
PMCPMC3175225
OpenAlexW2044822003

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Registered trials

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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.