Evidence map›Paper›PMID 32841603›Full record

ArticleCell2020

Large-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer.

Sarah E Johnstone, Alejandro Reyes, Yifeng Qi, Carmen Adriaens, Esmat Hegazi, Karin Pelka, Jonathan H Chen, Luli S Zou, Yotam Drier, Vivian Hecht and 11 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing papers in PubMed
13.0field-weighted citation impact, top 1% 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

142 citing papers in PubMed, 249 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 4 institutions in 2 countries.

Sarah E JohnstoneDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Alejandro ReyesBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
Yifeng QiBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Carmen AdriaensDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Esmat HegaziDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Karin PelkaBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Jonathan H ChenDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Luli S ZouBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
Yotam DrierThe Lautenberg Center for Immunology and Cancer Research, The Hebrew University, Jerusalem, Israel.
Vivian HechtBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Noam ShoreshBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Martin K SeligDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Caleb A LareauDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02215, USA.
Sowmya IyerDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Son C NguyenDepartment of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Eric F JoyceDepartment of Genetics, Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.
Rafael A IrizarryBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA.
Bin ZhangBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Martin J AryeeDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02215, USA. Electronic address: aryee.martin@mgh.harvard.edu.
Bradley E BernsteinDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA. Electronic address: bernstein.bradley@mgh.harvard.edu.
Broad Institute · USHarvard University · USUniversity of Pennsylvania · USHebrew University of Jerusalem · IL

Funding

MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
Epigenetic plasticity in tumor initiation and evolutionDP1CA216873 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BERNSTEIN, BRADLEY EVAN · 2016 to 2020
$5.9M
Preprocessing and Analysis Tools for High-Throughput TechnologiesR01GM083084 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2007 to 2018
$4.4M
Regulation of chromatin folding in space and timeR35GM128903 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Eric F. Joyce · 2018 to 2026
$4.2M
Data Analysis Tools for Emerging High-Throughput TechnologiesR35GM131802 · NIGMS · DANA-FARBER CANCER INST · PI Rafael Angel Irizarry · 2019 to 2026
$4.1M
Joint Interdisciplinary Training Program in Biostatistics & Computational BiologyT32GM074897 · NIGMS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HUTTENHOWER, CURTIS, LIN, XIHONG · 2005 to 2019
$3.7M
Overcoming bias and unwanted variability in next generation sequencingR01HG005220 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI IRIZARRY, RAFAEL ANGEL · 2010 to 2018
$3.6M
Probing and Perturbing Transcriptional Condensates with Multiscale Modeling and Deep LearningR35GM133580 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Bin Zhang · 2019 to 2026
$3.1M
Cancer Immunology Training GrantT32CA207021 · NCI · DANA-FARBER CANCER INST · PI WUCHERPFENNIG, KAI W · 2016 to 2020
$2.4M
NCI NIH HHS DP1 CA216873NCI NIH HHS T32 CA009216NCI NIH HHS T32 CA207021NHGRI NIH HHS R01 HG005220NIGMS NIH HHS R01 GM083084NIGMS NIH HHS R35 GM128903NIGMS NIH HHS R35 GM131802NIGMS NIH HHS R35 GM133580NIGMS NIH HHS T32 GM074897
6 · The paper itself

Abstract

Widespread changes to DNA methylation and chromatin are well documented in cancer, but the fate of higher-order chromosomal structure remains obscure. Here we integrated topological maps for colon tumors and normal colons with epigenetic, transcriptional, and imaging data to characterize alterations to chromatin loops, topologically associated domains, and large-scale compartments. We found that spatial partitioning of the open and closed genome compartments is profoundly compromised in tumors. This reorganization is accompanied by compartment-specific hypomethylation and chromatin changes. Additionally, we identify a compartment at the interface between the canonical A and B compartments that is reorganized in tumors. Remarkably, similar shifts were evident in non-malignant cells that have accumulated excess divisions. Our analyses suggest that these topological changes repress stemness and invasion programs while inducing anti-tumor immunity genes and may therefore restrain malignant progression. Our findings call into question the conventional view that tumor-associated epigenomic alterations are primarily oncogenic.

Indexed as

DNA MethylationEpigenesis, GeneticCell DivisionCellular SenescenceChromatinChromatin Immunoprecipitation SequencingChromosomesCohort StudiesColorectal NeoplasmsComputational BiologyEpigenomicsGene Expression Regulation, NeoplasticHCT116 CellsHumansIn Situ Hybridization, FluorescenceMicroscopy, Electron, TransmissionChromatinTumor Suppressor Proteinschromatincolon cancercompartmentDNA methylationepigeneticsgenome topologynuclear architecture

Identifiers

PMID32841603
PMCPMC7575124
OpenAlexW3080563305

What OpenQuestion holds

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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.