Evidence map›Paper›PMID 31930530›Full record

ArticleThe EMBO journal2020

In situ CRISPR-Cas9 base editing for the development of genetically engineered mouse models of breast cancer.

Stefano Annunziato, Catrin Lutz, Linda Henneman, Jinhyuk Bhin, Kim Wong, Bjørn Siteur, Bas van Gerwen, Renske de Korte-Grimmerink, Maria Paz Zafra, Emma M Schatoff and 11 more

Abstract read
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
–field-weighted citation impact
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

43 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Rat Models of Breast Cancer.Advances in experimental medicine and biology · 2025
    Review
  7. Leveraging preclinical models of metastatic breast cancer.Biochimica et biophysica acta. Reviews on cancer · 2024
    Review
  8. Rat Models of Hormone Receptor-Positive Breast Cancer.Journal of mammary gland biology and neoplasia · 2024
    Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Advances in Immunocompetent Mouse and Rat Models.Cold Spring Harbor perspectives in medicine · 2024
    Review
  15. Article
  16. Review
  17. Review
  18. CRISPR applications in cancer diagnosis and treatment.Cellular & molecular biology letters · 2023
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Stefano Annunziato *Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Catrin Lutz *Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Linda HennemanTransgenic Core Facility, Mouse Clinic for Cancer and Aging (MCCA), The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jinhyuk BhinDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Kim WongWellcome Trust Sanger Institute, Cambridge, UK.
Bjørn SiteurPreclinical Intervention Unit, Mouse Clinic for Cancer and Aging (MCCA), The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Bas van GerwenPreclinical Intervention Unit, Mouse Clinic for Cancer and Aging (MCCA), The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Renske de Korte-GrimmerinkPreclinical Intervention Unit, Mouse Clinic for Cancer and Aging (MCCA), The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Maria Paz ZafraDivision of Hematology and Medical Oncology, Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Emma M SchatoffDivision of Hematology and Medical Oncology, Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Anne Paulien DrenthDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Eline van der BurgDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Timo EijkmanDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Siddhartha MukherjeeDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Katharina BoroviakWellcome Trust Sanger Institute, Cambridge, UK.
Lodewyk Fa WesselsCancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Marieke van de VenPreclinical Intervention Unit, Mouse Clinic for Cancer and Aging (MCCA), The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Ivo J HuijbersTransgenic Core Facility, Mouse Clinic for Cancer and Aging (MCCA), The Netherlands Cancer Institute, Amsterdam, The Netherlands.
David J AdamsWellcome Trust Sanger Institute, Cambridge, UK.
Lukas E DowDivision of Hematology and Medical Oncology, Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Jos JonkersDivision of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-9264-9792

Funding

Targeting the WNT Pathway in Colorectal CancerF31CA224800 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHATOFF, EMMA M · 2017 to 2020
$179k
Cancer Genomics Netherlands (CGCNL) 024001028Cancer Systems Biology Center (CSBC) 85300120EC | FP7 | FP7 Ideas: European Research Council (FP7 Ideas)ERC Synergy project CombatCancer 319661National Roadmap grant for Large-Scale Research Facilities 184032303NCI NIH HHS F31 CA224800Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) VICI 91814643Netherlands Genomics Initiative (NGI) Zenith 93512009Oncode Institute
6 · The paper itself

Abstract

Genetically engineered mouse models (GEMMs) of cancer have proven to be of great value for basic and translational research. Although CRISPR-based gene disruption offers a fast-track approach for perturbing gene function and circumvents certain limitations of standard GEMM development, it does not provide a flexible platform for recapitulating clinically relevant missense mutations in vivo. To this end, we generated knock-in mice with Cre-conditional expression of a cytidine base editor and tested their utility for precise somatic engineering of missense mutations in key cancer drivers. Upon intraductal delivery of sgRNA-encoding vectors, we could install point mutations with high efficiency in one or multiple endogenous genes in situ and assess the effect of defined allelic variants on mammary tumorigenesis. While the system also produces bystander insertions and deletions that can stochastically be selected for when targeting a tumor suppressor gene, we could effectively recapitulate oncogenic nonsense mutations. We successfully applied this system in a model of triple-negative breast cancer, providing the proof of concept for extending this flexible somatic base editing platform to other tissues and tumor types.

Indexed as

Breast NeoplasmsCRISPR-Cas SystemsGene EditingAnimalsDisease Models, AnimalFemaleMiceMice, TransgenicMutationbase editingbreast cancerCRISPR-Cas9genetically engineered mouse modelsintraductal injections

Identifiers

PMID31930530
PMCPMC7049816

What OpenQuestion holds

Textmetadata
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.