Evidence map›Paper›PMID 26052355›Full record

ArticleClinical epigenetics2015

The GALNT9, BNC1 and CCDC8 genes are frequently epigenetically dysregulated in breast tumours that metastasise to the brain.

Rajendra P Pangeni, Prasanna Channathodiyil, David S Huen, Lawrence W Eagles, Balraj K Johal, Dawar Pasha, Natasa Hadjistephanou, Oliver Nevell, Claire L Davies, Ayobami I Adewumi and 15 more

Open access · goldAbstract read
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 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
3.6field-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

59 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Towards updated understanding of brain metastasis.American journal of cancer research · 2022
    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

25 authors at 7 institutions in 2 countries.

Rajendra P PangeniBrain Tumour Research Centre, University of Wolverhampton, Wolverhampton, UK.
Prasanna ChannathodiyilBrain Tumour Research Centre, University of Wolverhampton, Wolverhampton, UK.
David S HuenSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Lawrence W EaglesBrain Tumour Research Centre, University of Wolverhampton, Wolverhampton, UK.
Balraj K JohalSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Dawar PashaSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Natasa HadjistephanouSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Oliver NevellSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Claire L DaviesSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Ayobami I AdewumiSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Hamida KhanomSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Ikroop S SamraSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Vanessa C BuzattoSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Preethi ChandrasekaranSchool of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK.
Thoraia ShinawiCentre for Rare Diseases and Personalised Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Timothy P DawsonDepartment of Neurosciences, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood, Preston, UK.
Katherine M AshtonDepartment of Neurosciences, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood, Preston, UK.
Charles DavisDepartment of Neurosciences, Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital, Fulwood, Preston, UK.
Andrew R BrodbeltThe Walton Centre NHS Foundation Trust, Lower Lane, Liverpool, UK.
Michael D JenkinsonThe Walton Centre NHS Foundation Trust, Lower Lane, Liverpool, UK.
Ivan BiècheDepartment of Genetics, Institute Curie, Paris, France.
Farida LatifCentre for Rare Diseases and Personalised Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
John L DarlingBrain Tumour Research Centre, University of Wolverhampton, Wolverhampton, UK.
Tracy J WarrBrain Tumour Research Centre, University of Wolverhampton, Wolverhampton, UK.
Mark R MorrisBrain Tumour Research Centre, University of Wolverhampton, Wolverhampton, UK ; School of Biology, Chemistry and Forensic Sciences, University of Wolverhampton, Wolverhampton, UK ; Centre for Rare Diseases and Personalised Medicine, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
University of Wolverhampton · GBUniversity of Birmingham · GBBrain Tumour Research · GBLancashire Teaching Hospitals NHS Foundation Trust · GBUniversity of Liverpool · GBInstitut Curie · FRRoyal Preston Hospital · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumour metastasis to the brain is a common and deadly development in certain cancers; 18-30 % of breast tumours metastasise to the brain. The contribution that gene silencing through epigenetic mechanisms plays in these metastatic tumours is not well understood.

resultsWe have carried out a bioinformatic screen of genome-wide breast tumour methylation data available at The Cancer Genome Atlas (TCGA) and a broad literature review to identify candidate genes that may contribute to breast to brain metastasis (BBM). This analysis identified 82 candidates. We investigated the methylation status of these genes using Combined Bisulfite and Restriction Analysis (CoBRA) and identified 21 genes frequently methylated in BBM. We have identified three genes, GALNT9, CCDC8 and BNC1, that were frequently methylated (55, 73 and 71 %, respectively) and silenced in BBM and infrequently methylated in primary breast tumours. CCDC8 was commonly methylated in brain metastases and their associated primary tumours whereas GALNT9 and BNC1 were methylated and silenced only in brain metastases, but not in the associated primary breast tumours from individual patients. This suggests differing roles for these genes in the evolution of metastatic tumours; CCDC8 methylation occurs at an early stage of metastatic evolution whereas methylation of GANLT9 and BNC1 occurs at a later stage of tumour evolution. Knockdown of these genes by RNAi resulted in a significant increase in the migratory and invasive potential of breast cancer cell lines.

conclusionsThese findings indicate that GALNT9 (an initiator of O-glycosylation), CCDC8 (a regulator of microtubule dynamics) and BNC1 (a transcription factor with a broad range of targets) may play a role in the progression of primary breast tumours to brain metastases. These genes may be useful as prognostic markers and their products may provide novel therapeutic targets.

Indexed as

BrainBreastDNA methylationEpigeneticMetastasisTumour suppressor

Identifiers

PMID26052355
PMCPMC4457099
OpenAlexW1564613369

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.