Evidence map›Paper›PMID 26884349›Full record

ArticleBMC cancer2016

Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients.

Andrea J Savio, Darshana Daftary, Elizabeth Dicks, Daniel D Buchanan, Patrick S Parfrey, Joanne P Young, Daniel Weisenberger, Roger C Green, Steven Gallinger, John R McLaughlin and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

3 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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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 6 institutions in 3 countries.

Andrea J SavioDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. savio@lunenfeld.ca.
Darshana DaftaryLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. daftary@lunenfeld.ca.
Elizabeth DicksFaculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada. edicks@mun.ca.
Daniel D BuchananOncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia. daniel.buchanan@unimelb.edu.au.
Patrick S ParfreyFaculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada. pparfrey@mun.ca.
Joanne P YoungDepartment of Haematology and Oncology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia. joanne.young@adelaide.edu.au.
Daniel WeisenbergerUSC Epigenome Center, University of Southern California, Los Angeles, CA, USA. dan.weisenberger@med.usc.edu.
Roger C GreenFaculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada. rcgreen@mun.ca.
Steven GallingerDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. steven.gallinger@uhn.ca.
John R McLaughlinLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. john.mclaughlin@oahpp.ca.
Julia A KnightLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. knight@lunenfeld.ca.
Bharati BapatDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. bapat@lunenfeld.ca.
Lunenfeld-Tanenbaum Research Institute · CAMemorial University of Newfoundland · CAQueen Elizabeth Hospital · AUUniversity of Melbourne · AUUniversity of Southern California · USUniversity of Toronto · CA

Funding

ONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCERU01CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 1997 to 2008
$12.5M
Colon Cancer Family Registry CohortUM1CA167551 · NCI · STANFORD UNIVERSITY · PI HAILE, ROBERT WILLIAM, JENKINS, MARK A · 2013 to 2017
$11.3M
AUSTRALASIAN COLORECTAL CANCER FAMILY REGISTRYU01CA097735 · NCI · UNIVERSITY OF MELBOURNE · PI HOPPER, JOHN L · 2002 to 2007
$6.9M
The Colon Cancer Family Registry: AustralasiaU24CA097735 · NCI · UNIVERSITY OF MELBOURNE · PI HOPPER, JOHN L · 2008 to 2011
$6.2M
The Colon Cancer Family Registry: OntarioU24CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 2008 to 2011
$4.1M
Redox Regulation of Metastasis by Sod2K22CA095011 · NCI · ALBANY MEDICAL COLLEGE · PI MELENDEZ, JUAN ANDRES · 2002 to 2004
$446k
Canadian Institutes of Health Research CTP-79845NCI NIH HHS CA-95-011NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA097735NCI NIH HHS U01/U24 CA074783NCI NIH HHS U01/U24 CA097735NCI NIH HHS U24 CA074783NCI NIH HHS U24 CA097735NCI NIH HHS UM1 CA167551
6 · The paper itself

Abstract

backgroundAberrant Wnt signaling activation occurs commonly in colorectal carcinogenesis, leading to upregulation of many target genes. APC (adenomatous polyposis coli) is an important component of the β-catenin destruction complex, which regulates Wnt signaling, and is often mutated in colorectal cancer (CRC). In addition to mutational events, epigenetic changes arise frequently in CRC, specifically, promoter hypermethylation which silences tumor suppressor genes. APC and the Wnt signaling target gene ITF2 (immunoglobulin transcription factor 2) incur hypermethylation in various cancers, however, methylation-dependent regulation of these genes in CRC has not been studied in large, well-characterized patient cohorts. The microsatellite instability (MSI) subtype of CRC, featuring DNA mismatch repair deficiency and often promoter hypermethylation of MutL homolog 1 (MLH1), has a favorable outcome and is characterized by different chemotherapeutic responses than microsatellite stable (MSS) tumors. Other epigenetic events distinguishing these subtypes have not yet been fully elucidated.

methodsHere, we quantify promoter methylation of ITF2 and APC by MethyLight in two case-case studies nested in population-based CRC cohorts from the Ontario Familial Colorectal Cancer Registry (n = 330) and the Newfoundland Familial Colorectal Cancer Registry (n = 102) comparing MSI status groups.

resultsITF2 and APC methylation are significantly associated with tumor versus normal state (both P < 1.0 × 10(-6)). ITF2 is methylated in 45.8% of MSI cases and 26.9% of MSS cases and is significantly associated with MSI in Ontario (P = 0.002) and Newfoundland (P = 0.005) as well as the MSI-associated feature of MLH1 promoter hypermethylation (P = 6.72 × 10(-4)). APC methylation, although tumor-specific, does not show a significant association with tumor subtype, age, gender, or stage, indicating it is a general tumor-specific CRC biomarker.

conclusionsThis study demonstrates, for the first time, MSI-associated ITF2 methylation, and further reveals the subtype-specific epigenetic events modulating Wnt signaling in CRC.

Indexed as

Microsatellite InstabilityAdenomatous Polyposis Coli ProteinBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCohort StudiesColonColorectal NeoplasmsDNA MethylationFemaleHumansMaleMiddle AgedPromoter Regions, GeneticTranscription Factor 4Transcription FactorsWnt Signaling PathwayAdenomatous Polyposis Coli ProteinAPC protein, humanBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsTCF4 protein, humanTranscription Factor 4Transcription Factors

Identifiers

PMID26884349
PMCPMC4756469
OpenAlexW2274120501

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.