Evidence map›Paper›PMID 23284750›Full record

ArticlePloS one2012

Epigenetic changes in Basal Cell Carcinoma affect SHH and WNT signaling components.

Tjinta Brinkhuizen, Karin van den Hurk, Véronique J L Winnepenninckx, Joep P de Hoon, Ariënne M van Marion, Jürgen Veeck, Manon van Engeland, Maurice A M van Steensel

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
  2. Article
  3. Wnt Signaling Pathways: From Inflammation to Non-Melanoma Skin Cancers.International journal of molecular sciences · 2023
    Review
  4. Review
  5. Epigenetic Alterations in Keratinocyte Carcinoma.The Journal of investigative dermatology · 2021
    Article
  6. Article
  7. Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas.Cellular and molecular life sciences : CMLS · 2020
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Epigenetic regulation of epidermal differentiation.Cold Spring Harbor perspectives in medicine · 2014
    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

8 authors at 3 institutions in 2 countries.

Tjinta BrinkhuizenDepartment of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands. t.brinkhuizen@mumc.nl
Karin van den Hurk
Véronique J L Winnepenninckx
Joep P de Hoon
Ariënne M van Marion
Jürgen Veeck
Manon van Engeland
Maurice A M van Steensel
Maastricht University · NLMaastricht University Medical Centre · NLVieCuri Medisch Centrum · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe genetic background of Basal Cell Carcinoma (BCC) has been studied extensively, while its epigenetic makeup has received comparatively little attention. Epigenetic alterations such as promoter hypermethylation silence tumor suppressor genes (TSG) in several malignancies.

objectiveWe sought to analyze the promoter methylation status of ten putative (tumor suppressor) genes that are associated with Sonic Hedgehog (SHH), WNT signaling and (hair follicle) tumors in a large series of 112 BCC and 124 healthy control samples by methylation-specific PCR.

resultsGene promoters of SHH (P = 0.016), adenomatous polyposis coli (APC) (P = 0.003), secreted frizzled-related protein 5 (SFRP5) (P = 0.004) and Ras association domain family 1A (RASSF1A) (P = 0.023) showed significantly more methylation in BCC versus normal skin. mRNA levels of these four genes were reduced for APC and SFRP5 in BCC (n = 6) vs normal skin (n = 6). Down regulation of SHH, APC and RASSF1A could be confirmed on protein level as well (P<0.001 for all genes) by immunohistochemical staining. Increased canonical WNT activity was visualized by β-catenin staining, showing nuclear β-catenin in only 28/101 (27.7%) of BCC. Absence of nuclear β-catenin in some samples may be due to high levels of membranous E-cadherin (in 94.1% of the samples).

conclusionsWe provide evidence that promoter hypermethylation of key players within the SHH and WNT pathways is frequent in BCC, consistent with their known constitutive activation in BCC. Epigenetic gene silencing putatively contributes to BCC tumorigenesis, indicating new venues for treatment.

Indexed as

DNA MethylationEpigenesis, GeneticAgedBasal Cell CarcinomaCase-Control StudiesFemaleGene Expression Regulation, NeoplasticHedgehog ProteinsHumansMalePromoter Regions, GeneticSkinSkin NeoplasmsTumor Cells, CulturedTumor Suppressor ProteinsWnt ProteinsHedgehog ProteinsSHH protein, humanTumor Suppressor ProteinsWnt Proteins

Identifiers

PMID23284750
PMCPMC3524166
OpenAlexW1989652769

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.