Evidence map›Paper›PMID 19470733›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009

DNMT3B expression might contribute to CpG island methylator phenotype in colorectal cancer.

Katsuhiko Nosho, Kaori Shima, Natsumi Irahara, Shoko Kure, Yoshifumi Baba, Gregory J Kirkner, Li Chen, Sumita Gokhale, Aditi Hazra, Donna Spiegelman and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Gene expression profiling predicts the development of oral cancer.Cancer prevention research (Philadelphia, Pa.) · 2011
    Trial
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  6. The role of tumor-associated macrophages in tumor immune evasion.Journal of cancer research and clinical oncology · 2024
    Review
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13 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

14 authors at 4 institutions in 1 country.

Katsuhiko NoshoDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Kaori Shima
Natsumi Irahara
Shoko Kure
Yoshifumi Baba
Gregory J Kirkner
Li Chen
Sumita Gokhale
Aditi Hazra
Donna Spiegelman
Edward L Giovannucci
Rudolf Jaenisch
Charles S Fuchs
Shuji Ogino
Harvard University · USDana-Farber Cancer Institute · USMassachusetts Institute of Technology · USProvidence College · US

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI TWOROGER, SHELLEY S · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI GIOVANNUCCI, EDWARD · 1991 to 2009
$41.8M
Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
New Methods for the design and evaluation of large HIV prevention interventionsR01AI112339 · NIAID · YALE UNIVERSITY · PI SPIEGELMAN, DONNA L · 2014 to 2017
$2.7M
Molecular Epidemiology of Colorectal CancerK07CA122826 · NCI · DANA-FARBER CANCER INST · PI OGINO, SHUJI · 2007 to 2010
$634k
NCI NIH HHS K07 CA122826NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS P01 CA55075NCI NIH HHS P01 CA87969NCI NIH HHS P50 CA127003NIAID NIH HHS R01 AI112339
6 · The paper itself

Abstract

purposeDNA methyltransferase-3B (DNMT3B) plays an important role in de novo CpG island methylation. Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colon cancer. EXPERIMENTAL

designUtilizing 765 colorectal cancers in two cohort studies, we detected DNMT3B expression in 116 (15%) tumors by immunohistochemistry. We assessed microsatellite instability, quantified DNA methylation in repetitive long interspersed nucleotide element-1 (LINE-1) by Pyrosequencing, eight CIMP-specific promoters [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1], and eight other CpG islands (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN) by real-time PCR (MethyLight).

resultsTumoral DNMT3B overexpression was significantly associated with CIMP-high [> or =6/8 methylated CIMP-specific promoters; odds ratio (OR), 3.34; 95% confidence interval, 2.11-5.29; P < 0.0001]. The relations between DNMT3B and methylation in 16 individual CpG islands varied substantially (OR, 0.80-2.96), suggesting variable locus-to-locus specificities of DNMT3B activity. DNMT3B expression was not significantly related with LINE-1 hypomethylation. In multivariate logistic regression, the significant relation between DNMT3B and CIMP-high persisted (OR, 2.39; 95% confidence interval, 1.11-5.14; P = 0.026) after adjusting for clinical and other molecular features, including p53, beta-catenin, LINE-1, microsatellite instability, KRAS, PIK3CA, and BRAF. DNMT3B expression was unrelated with patient outcome, survival, or prognosis.

conclusionsTumoral DNMT3B overexpression is associated with CIMP-high in colorectal cancer. Our data support a possible role of DNMT3B in nonrandom de novo CpG island methylation leading to colorectal cancer.

Indexed as

DNA MethylationAgedbeta CateninCohort StudiesColorectal NeoplasmsCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BFemaleHumansImmunohistochemistryLogistic ModelsLong Interspersed Nucleotide ElementsMaleMiddle AgedModels, Biologicalbeta CateninDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3BTumor Suppressor Protein p53

Identifiers

PMID19470733
PMCPMC2866637
OpenAlexW2096139566

What OpenQuestion holds

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LicenceTDM
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.