Evidence map›Paper›PMID 24485021›Full record

ArticleBMC cancer2014

A panel of genes methylated with high frequency in colorectal cancer.

Susan M Mitchell, Jason P Ross, Horace R Drew, Thu Ho, Glenn S Brown, Neil F W Saunders, Konsta R Duesing, Michael J Buckley, Rob Dunne, Iain Beetson and 10 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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

114 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

54 more citing papers are in PubMed but not listed here.

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

20 authors at 3 institutions in 1 country.

Susan M Mitchell
Jason P Ross
Horace R Drew
Thu Ho
Glenn S Brown
Neil F W Saunders
Konsta R Duesing
Michael J Buckley
Rob Dunne
Iain Beetson
Keith N Rand
Aidan McEvoy
Melissa L Thomas
Rohan T Baker
David A Wattchow
Graeme P Young
Trevor J Lockett
Susanne K Pedersen
Lawrence C Lapointe
Peter L MolloyCSIRO Animal, Food & Health Sciences, Preventative Health Flagship, North Ryde, NSW, Australia. peter.molloy@csiro.au.
Commonwealth Scientific and Industrial Research Organisation · AUAnimal, Food and Health Sciences · AUFlinders University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests.

methodsCombined epigenomic methods - activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment - were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP).

resultsCombined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in >50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas.

conclusionsThis study has characterised a panel of 23 genes that show elevated DNA methylation in >50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers.

Indexed as

Gene Expression Regulation, NeoplasticBiomarkers, TumorColorectal NeoplasmsDNA MethylationGenetic Association StudiesHCT116 CellsHT29 CellsHumansBiomarkers, Tumor

Identifiers

PMID24485021
PMCPMC3924905
OpenAlexW2018115135

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.