Evidence map›Paper›PMID 26806129›Full record

ArticleCell2016

Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair.

Nicholas J Haradhvala, Paz Polak, Petar Stojanov, Kyle R Covington, Eve Shinbrot, Julian M Hess, Esther Rheinbay, Jaegil Kim, Yosef E Maruvka, Lior Z Braunstein and 6 more

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

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 284 papers.

0numbers the graph read from it
0cells of the map it votes in
284citing papers in PubMed
31.0field-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

284 citing papers in PubMed, 439 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Distinct repair processes produce APOBEC-induced deletions, tandem substitutions, and complex mutations in yeast and human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Topographical archetypes of somatic mutagenesis in cancer.bioRxiv : the preprint server for biology · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Divergent somatic mutation patterns among human cerebellar neuron types.bioRxiv : the preprint server for biology · 2025
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

224 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

16 authors at 6 institutions in 1 country.

Nicholas J HaradhvalaMassachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Paz PolakMassachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
Petar StojanovCarnegie Mellon University School of Computer Science, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA.
Kyle R CovingtonBaylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Eve ShinbrotBaylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Julian M HessBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Esther RheinbayMassachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Jaegil KimBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Yosef E MaruvkaMassachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Lior Z BraunsteinBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
Atanas KamburovMassachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
Philip C HanawaltStanford University Department of Biology, 450 Serra Mall, Stanford, CA 94305, USA.
David A WheelerBaylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Amnon KorenBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Cornell University Department of Molecular Biology and Genetics, 526 Campus Road, Ithaca, NY 14853, USA.
Michael S LawrenceBroad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA. Electronic address: lawrence@broadinstitute.org.
Gad GetzMassachusetts General Hospital Cancer Center and Department of Pathology, 55 Fruit Street, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: gadgetz@broadinstitute.org.
Broad Institute · USBaylor College of Medicine · USMassachusetts General Hospital · USCarnegie Mellon University · USLemuel Shattuck Hospital · USStanford University · US

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
The Cancer Genome Atlas Data Analysis CenterU24CA143845 · NCI · BROAD INSTITUTE, INC. · PI CHIN, LYNDA, GETZ, GAD A · 2009 to 2016
$16.0M
Role of transcription in genomic stabilityR01CA077712 · NCI · STANFORD UNIVERSITY · PI HANAWALT, PHILIP COURTLAND · 1998 to 2016
$5.6M
NCI NIH HHS R01 CA077712NCI NIH HHS U24 CA143845NCI NIH HHS U24CA143845NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54HG003067NHGRI NIH HHS U54 HG003273NHGRI NIH HHS U54HG003273
6 · The paper itself

Abstract

Mutational processes constantly shape the somatic genome, leading to immunity, aging, cancer, and other diseases. When cancer is the outcome, we are afforded a glimpse into these processes by the clonal expansion of the malignant cell. Here, we characterize a less explored layer of the mutational landscape of cancer: mutational asymmetries between the two DNA strands. Analyzing whole-genome sequences of 590 tumors from 14 different cancer types, we reveal widespread asymmetries across mutagenic processes, with transcriptional ("T-class") asymmetry dominating UV-, smoking-, and liver-cancer-associated mutations and replicative ("R-class") asymmetry dominating POLE-, APOBEC-, and MSI-associated mutations. We report a striking phenomenon of transcription-coupled damage (TCD) on the non-transcribed DNA strand and provide evidence that APOBEC mutagenesis occurs on the lagging-strand template during DNA replication. As more genomes are sequenced, studying and classifying their asymmetries will illuminate the underlying biological mechanisms of DNA damage and repair.

Indexed as

DNA DamageDNA Mutational AnalysisDNA RepairDNA ReplicationGenome, HumanGenome-Wide Association StudyHumansMutationNeoplasmsTranscription, Genetic

Identifiers

PMID26806129
PMCPMC4753048
OpenAlexW2266041843

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.