Evidence map›Paper›PMID 34764240›Full record

ArticleNature communications2021

A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing.

Sanju Sinha, Karina Barbosa, Kuoyuan Cheng, Mark D M Leiserson, Prashant Jain, Anagha Deshpande, David M Wilson, Bríd M Ryan, Ji Luo, Ze'ev A Ronai and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Epigenetic editing of marine medaka (Zoological research · 2026
    Article
  8. Article
  9. Genes & diseases · 2026
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Synthetic Cells and Molecules in Cellular Immunotherapy.International journal of biological sciences · 2024
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Sanju Sinha *Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Karina Barbosa *Tumor Initiation Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.ORCID http://orcid.org/0000-0002-6233-3332
Kuoyuan Cheng *Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Mark D M LeisersonCenter for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, 20742, USA.
Prashant JainTumor Initiation Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Anagha DeshpandeTumor Initiation Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
David M WilsonLaboratory of Molecular Gerontology, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD, 21224, USA.
Bríd M RyanLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20850, USA.ORCID http://orcid.org/0000-0003-0038-131X
Ji LuoLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, 20850, USA.ORCID http://orcid.org/0000-0001-5063-1626
Ze'ev A RonaiTumor Initiation Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Joo Sang LeeSamsung Medical Center, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.ORCID http://orcid.org/0000-0001-8564-0848
Aniruddha J DeshpandeTumor Initiation Program, Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. adeshpande@sbpdiscovery.org.ORCID http://orcid.org/0000-0002-5240-9356
Eytan RuppinCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. eytan.ruppin@nih.gov.
National Institutes of Health · USSanford Burnham Prebys Medical Discovery Institute · USNational Cancer Institute · USSamsung Medical Center · KRUniversity of Maryland, College Park · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
Rewired Signaling at the Nexus of Melanoma Metastasis and ResistanceR35CA197465 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RONAI, ZEEV A. · 2016 to 2022
$7.9M
NCI NIH HHS P30 CA030199NCI NIH HHS R35 CA197465
6 · The paper itself

Abstract

Recent studies have reported that genome editing by CRISPR-Cas9 induces a DNA damage response mediated by p53 in primary cells hampering their growth. This could lead to a selection of cells with pre-existing p53 mutations. In this study, employing an integrated computational and experimental framework, we systematically investigated the possibility of selection of additional cancer driver mutations during CRISPR-Cas9 gene editing. We first confirm the previous findings of the selection for pre-existing p53 mutations by CRISPR-Cas9. We next demonstrate that similar to p53, wildtype KRAS may also hamper the growth of Cas9-edited cells, potentially conferring a selective advantage to pre-existing KRAS-mutant cells. These selective effects are widespread, extending across cell-types and methods of CRISPR-Cas9 delivery and the strength of selection depends on the sgRNA sequence and the gene being edited. The selection for pre-existing p53 or KRAS mutations may confound CRISPR-Cas9 screens in cancer cells and more importantly, calls for monitoring patients undergoing CRISPR-Cas9-based editing for clinical therapeutics for pre-existing p53 and KRAS mutations.

Indexed as

Computational BiologyCRISPR-Associated Protein 9Gene EditingHumansMutationProto-Oncogene Proteins p21(ras)CRISPR-Associated Protein 9KRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID34764240
PMCPMC8586238
OpenAlexW3132222706

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.