Evidence map›Paper›PMID 24837369›Full record

ArticleOncogene2015

Inhibition of intestinal tumor formation by deletion of the DNA methyltransferase 3a.

B Weis, J Schmidt, H Maamar, A Raj, H Lin, C Tóth, K Riedmann, G Raddatz, H-K Seitz, A D Ho and 2 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  9. Functional Versatility of the CDK Inhibitor p57Frontiers in cell and developmental biology · 2020
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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

12 authors at 4 institutions in 2 countries.

B WeisDivision of Epigenetics (A130), German Cancer Research Center (DKFZ), Heidelberg, Germany.
J SchmidtDivision of Epigenetics (A130), German Cancer Research Center (DKFZ), Heidelberg, Germany.
H MaamarDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
A RajDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
H LinDepartment of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
C Tóth1] Department of Pathology, University of Heidelberg, National Center for Tumor Diseases (NCT) Tissue Bank, Heidelberg, Germany [2] Department of Pathology, Heinrich Heine University, Düsseldorf, Germany.
K RiedmannDivision of Epigenetics (A130), German Cancer Research Center (DKFZ), Heidelberg, Germany.
G RaddatzDivision of Epigenetics (A130), German Cancer Research Center (DKFZ), Heidelberg, Germany.
H-K SeitzDepartment of Medicine, Salem Medical Center, Alcohol Research Center, University of Heidelberg, Heidelberg, Germany.
A D HoDepartment of Hematology/Oncology, University of Heidelberg Medical Center, Heidelberg, Germany.
F LykoDivision of Epigenetics (A130), German Cancer Research Center (DKFZ), Heidelberg, Germany.
H G Linhart1] Department of Medicine, Salem Medical Center, Alcohol Research Center, University of Heidelberg, Heidelberg, Germany [2] Department of Hematology/Oncology, University of Heidelberg Medical Center, Heidelberg, Germany [3] Division of Epigenetics (A130), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Heidelberg University · DEGerman Cancer Research Center · DEUniversity of Pennsylvania · USNational Center for Tumor Diseases · DE

Funding

A Comprehensive Spatial Picture of Transcription in the NucleusDP2OD008514 · OD · UNIVERSITY OF PENNSYLVANIA · PI RAJ, ARJUN · 2011 to 2011
$2.4M
NIH HHS 1DP2OD008514-01
6 · The paper itself

Abstract

Aberrant de novo methylation of DNA is considered an important mediator of tumorigenesis. To investigate the role of de novo DNA methyltransferase 3a (Dnmt3a) in intestinal tumor development, we analyzed the expression of Dnmt3a in murine colon crypts, murine colon adenomas and human colorectal cancer using RNA fluorescence in situ hybridization (FISH), quantitative PCR and immunostaining. Following conditional deletion of Dnmt3a in the colon of APC((Min/+)) mice, we analyzed tumor numbers, genotype of macroadenomas and laser dissected microadenomas, global and regional DNA methylation and gene expression. Our results showed increased Dnmt3a expression in colon adenomas of APC((Min/+)) mice and human colorectal cancer samples when compared with control tissue. Interestingly, in tumor tissue, RNA FISH analysis showed highest Dnmt3a expression in Lgr5-positive stem/progenitor cells. Deletion of Dnmt3a in APC((Min/+)) mice reduced colon tumor numbers by ~40%. Remaining adenomas and microadenomas almost exclusively contained the non-recombined Dnmt3a allele; no tumors composed of the inactivated Dnmt3a allele were detected. DNA methylation was reduced at the Oct4, Nanog, Tff2 and Cdkn1c promoters and expression of the tumor-suppressor genes Tff2 and Cdkn1c was increased. In conclusion, our results show that Dnmt3a is predominantly expressed in the stem/progenitor cell compartment of tumors and that deletion of Dnmt3a inhibits the earliest stages of intestinal tumor development.

Indexed as

AdenomaAnimalsCell Transformation, NeoplasticColonColorectal NeoplasmsCyclin-Dependent Kinase Inhibitor p57DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansIn Situ Hybridization, FluorescenceMiceMice, Inbred C57BLMice, TransgenicCdkn1c protein, mouseCyclin-Dependent Kinase Inhibitor p57DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanDnmt3a protein, mouseHomeodomain ProteinsMucinsMuscle ProteinsNanog Homeobox ProteinNanog protein, mouseOctamer Transcription Factor-3PeptidesPou5f1 protein, mouseTFF2 protein, humanTFF2 protein, mouseTrefoil Factor-2

Identifiers

PMID24837369
OpenAlexW1972878159

What OpenQuestion holds

Textmetadata
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.