Evidence map›Paper›PMID 26527001›Full record

ArticleCell reports2015

APOBEC-Induced Cancer Mutations Are Uniquely Enriched in Early-Replicating, Gene-Dense, and Active Chromatin Regions.

Marat D Kazanov, Steven A Roberts, Paz Polak, John Stamatoyannopoulos, Leszek J Klimczak, Dmitry A Gordenin, Shamil R Sunyaev

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

64 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
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  6. Action-at-a-distance mutations by 8-oxo-7,8-dihydroguanine: adenine pair triggered by MUTYH.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025
    Article
  7. Article
  8. Transcription-Replication Conflicts: Unlocking New Frontiers in Cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
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4 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

7 authors at 6 institutions in 2 countries.

Marat D KazanovResearch and Training Center on Bioinformatics, A.A. Kharkevich Institute for Information Transmission Problems, RAS, Moscow 127051, Russia.
Steven A RobertsNational Institute of Environmental Health Sciences, Durham, NC 27709, USA; School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Paz PolakDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
John StamatoyannopoulosDepartments of Genome Sciences and Medicine, University of Washington, Seattle, WA 98195, USA.
Leszek J KlimczakNational Institute of Environmental Health Sciences, Durham, NC 27709, USA.
Dmitry A GordeninNational Institute of Environmental Health Sciences, Durham, NC 27709, USA. Electronic address: gordenin@niehs.nih.gov.
Shamil R SunyaevDivision of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ssunyaev@rics.bwh.harvard.edu.
National Institute of Environmental Health Sciences · USBrigham and Women's Hospital · USHarvard University · USInstitute for Information Transmission Problems · RUUniversity of Washington · USWashington State University · US

Funding

Genome-wide hypermutation and structural instabilityZIAES103266 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI GORDENIN, DMITRY · 2015 to 2025
$18.0M
Statistical methods for studies of rare variantsR01MH101244 · NIMH · HARVARD MEDICAL SCHOOL · PI Benjamin Michael Neale, ALKES L PRICE · 2013 to 2026
$9.4M
New Methods and Enhanced Software for Predicting Functional SNPsR01GM078598 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SUNYAEV, SHAMIL · 2007 to 2017
$3.5M
Environmentally-modulated cytosine deamination in genome instability and cancerR00ES022633 · NIEHS · WASHINGTON STATE UNIVERSITY · PI ROBERTS, STEVEN A · 2015 to 2017
$868k
Intramural NIH HHS ZIA ES103266NIEHS NIH HHS 4R00ES022633-02NIEHS NIH HHS R00 ES022633NIGMS NIH HHS R01 GM078598NIMH NIH HHS R01 MH101244PHS HHS Z1AES103266
6 · The paper itself

Abstract

An antiviral component of the human innate immune system-the APOBEC cytidine deaminases-was recently identified as a prominent source of mutations in cancers. Here, we investigated the distribution of APOBEC-induced mutations across the genomes of 119 breast and 24 lung cancer samples. While the rate of most mutations is known to be elevated in late-replicating regions that are characterized by reduced chromatin accessibility and low gene density, we observed a marked enrichment of APOBEC mutations in early-replicating regions. This unusual mutagenesis profile may be associated with a higher propensity to form single-strand DNA substrates for APOBEC enzymes in early-replicating regions and should be accounted for in statistical analyses of cancer genome mutation catalogs aimed at understanding the mechanisms of carcinogenesis as well as highlighting genes that are significantly mutated in cancer.

Indexed as

DNA ReplicationMutation RateBreast NeoplasmsCytidine DeaminaseEuchromatinFemaleHumansLung NeoplasmsMCF-7 CellsMutationCytidine DeaminaseEuchromatin

Identifiers

PMID26527001
PMCPMC4644490
OpenAlexW2181759397

What OpenQuestion holds

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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.