Evidence map›Paper›PMID 32267900›Full record

ArticlePloS one2020

Interplay between TERT promoter mutations and methylation culminates in chromatin accessibility and TERT expression.

Catarina Salgado, Celine Roelse, Rogier Nell, Nelleke Gruis, Remco van Doorn, Pieter van der Velden

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Pan-cancer analysis of telomere maintenance mechanisms.The Journal of biological chemistry · 2024
    Article
  8. The C250T Mutation ofCancers · 2024
    Article
  9. Article
  10. Review
  11. Heliyon · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. TERT-Regulation and Roles in Cancer Formation.Frontiers in immunology · 2020
    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 1 institution in 1 country.

Catarina SalgadoDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-5926-855X
Celine RoelseDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Rogier NellDepartment of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Nelleke GruisDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-5210-9150
Remco van DoornDepartment of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.ORCID 0000-0002-7019-6673
Pieter van der VeldenDepartment of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The telomerase reverse transcriptase (TERT) gene is responsible for telomere maintenance in germline and stem cells, and is re-expressed in 90% of human cancers. CpG methylation in the TERT promoter (TERTp) was correlated with TERT mRNA expression. Furthermore, two hotspot mutations in TERTp, dubbed C228T and C250T, have been revealed to facilitate binding of transcription factor ETS/TCF and subsequent TERT expression. This study aimed to elucidate the combined contribution of epigenetic (promoter methylation and chromatin accessibility) and genetic (promoter mutations) mechanisms in regulating TERT gene expression in healthy skin samples and in melanoma cell lines (n = 61). We unexpectedly observed that the methylation of TERTp was as high in a subset of healthy skin cells, mainly keratinocytes, as in cutaneous melanoma cell lines. In spite of the high promoter methylation fraction in wild-type (WT) samples, TERT mRNA was only expressed in the melanoma cell lines with either high methylation or intermediate methylation in combination with TERT mutations. TERTp methylation was positively correlated with chromatin accessibility and TERT mRNA expression in 8 melanoma cell lines. Cooperation between epigenetic and genetic mechanisms were best observed in heterozygous mutant cell lines as chromosome accessibility preferentially concerned the mutant allele. Combined, these results suggest a complex model in which TERT expression requires either a widely open chromatin state in TERTp-WT samples due to high methylation throughout the promoter or a combination of moderate methylation fraction/chromatin accessibility in the presence of the C228T or C250T mutations.

Indexed as

DNA MethylationAllelesCell LineChromatinChromatin Assembly and DisassemblyCpG IslandsHumansKeratinocytesMelanomaMutationPromoter Regions, GeneticProtein BindingRNA, MessengerSkin NeoplasmsTelomeraseTranscription FactorsChromatinRNA, MessengerTelomeraseTERT protein, humanTranscription Factors

Identifiers

PMID32267900
PMCPMC7141627
OpenAlexW3014261301

What OpenQuestion holds

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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.