Evidence map›Paper›PMID 29945573›Full record

ArticleBMC cancer2018

Gene promoter and exon DNA methylation changes in colon cancer development - mRNA expression and tumor mutation alterations.

Béla Molnár, Orsolya Galamb, Bálint Péterfia, Barnabás Wichmann, István Csabai, András Bodor, Alexandra Kalmár, Krisztina Andrea Szigeti, Barbara Kinga Barták, Zsófia Brigitta Nagy and 4 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.2field-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

39 citing papers in PubMed, 68 citations in OpenAlex.

  1. A Novel Prognostic DNA Methylation Panel for Colorectal Cancer.International journal of molecular sciences · 2019
    Trial
  2. Uncovering alterations in cancer epigenetics via trans-dimensional Markov chain Monte Carlo and hidden Markov models.Journal of the Royal Statistical Society. Series C, Applied statistics · 2026
    Article
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  10. IncreasedPharmaceuticals (Basel, Switzerland) · 2024
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  15. Pharmaceuticals (Basel, Switzerland) · 2023
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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

14 authors at 4 institutions in 1 country.

Béla MolnárMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary. molnar.bela1@med.semmelweis-univ.hu.
Orsolya GalambMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary.
Bálint Péterfia2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, Budapest, H-1088, Hungary.
Barnabás WichmannMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary.
István CsabaiDepartment of Physics of Complex Systems, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary.
András BodorDepartment of Physics of Complex Systems, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, H-1117, Hungary.
Alexandra KalmárMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary.
Krisztina Andrea Szigeti2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, Budapest, H-1088, Hungary.
Barbara Kinga Barták2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, Budapest, H-1088, Hungary.
Zsófia Brigitta Nagy2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, Budapest, H-1088, Hungary.
Gábor ValczMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary.
Árpád V Patai2nd Department of Internal Medicine, Semmelweis University, Szentkirályi str 46, Budapest, H-1088, Hungary.
Péter IgazMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary.
Zsolt TulassayMolecular Medicine Research Group, Hungarian Academy of Sciences, Szentkirályi str 46, Budapest, H-1088, Hungary.
Semmelweis University · HUHungarian Academy of Sciences · HUEötvös Loránd University · HUUniversity of Pecs · HU

Funding

National Research, Development and Innovation Office KMR-12-1-2012-0216National Research, Development and Innovation Office NVKP_16-1-2016-0004Novo Nordisk Foundation Interdisciplinary Synergy Programme NNF15OC0016584Országos Tudományos Kutatási Alapprogramok OTKA-K111743
6 · The paper itself

Abstract

backgroundDNA mutations occur randomly and sporadically in growth-related genes, mostly on cytosines. Demethylation of cytosines may lead to genetic instability through spontaneous deamination. Aims were whole genome methylation and targeted mutation analysis of colorectal cancer (CRC)-related genes and mRNA expression analysis of TP53 pathway genes.

methodsLong interspersed nuclear element-1 (LINE-1) BS-PCR followed by pyrosequencing was performed for the estimation of global DNA metlyation levels along the colorectal normal-adenoma-carcinoma sequence. Methyl capture sequencing was done on 6 normal adjacent (NAT), 15 adenomatous (AD) and 9 CRC tissues. Overall quantitative methylation analysis, selection of top hyper/hypomethylated genes, methylation analysis on mutation regions and TP53 pathway gene promoters were performed. Mutations of 12 CRC-related genes (APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA, SMAD2, SMAD4, TP53) were evaluated. mRNA expression of TP53 pathway genes was also analyzed.

resultsAccording to the LINE-1 methylation results, overall hypomethylation was observed along the normal-adenoma-carcinoma sequence. Within top50 differential methylated regions (DMRs), in AD-N comparison TP73, NGFR, PDGFRA genes were hypermethylated, FMN1, SLC16A7 genes were hypomethylated. In CRC-N comparison DKK2, SDC2, SOX1 genes showed hypermethylation, while ERBB4, CREB5, CNTN1 genes were hypomethylated. In certain mutation hot spot regions significant DNA methylation alterations were detected. The TP53 gene body was addressed by hypermethylation in adenomas. APC, TP53 and KRAS mutations were found in 30, 15, 21% of adenomas, and in 29, 53, 29% of CRCs, respectively. mRNA expression changes were observed in several TP53 pathway genes showing promoter methylation alterations.

conclusionsDNA methylation with consecutive phenotypic effect can be observed in a high number of promoter and gene body regions through CRC development.

Indexed as

DNA MethylationExonsMutationPromoter Regions, GeneticAdenomaColorectal NeoplasmsCpG IslandsHumansLong Interspersed Nucleotide ElementsSignal TransductionTumor Suppressor Protein p53Tumor Suppressor Protein p53AdenomaColorectal cancerDNA methylationMethyl capture sequencingMutationTP53 signaling pathway

Identifiers

PMID29945573
PMCPMC6020382
OpenAlexW2811463598

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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.