Cited by 640CRISPR and Genetic EngineeringCancer Genomics and DiagnosticsLung Cancer Treatments and Mutations

The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.

In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system

Open access

Abstract

Chromosomal rearrangements have a central role in the pathogenesis of human cancers and often result in the expression of therapeutically actionable gene fusions. A recently discovered example is a fusion between the genes echinoderm microtubule-associated protein like 4 (EML4) and anaplastic lymphoma kinase (ALK), generated by an inversion on the short arm of chromosome 2: inv(2)(p21p23). The EML4-ALK oncogene is detected in a subset of human non-small cell lung cancers (NSCLC) and is clinically relevant because it confers sensitivity to ALK inhibitors. Despite their importance, modelling such genetic events in mice has proven challenging and requires complex manipulation of the germ line. Here we describe an efficient method to induce specific chromosomal rearrangements in vivo using viral-mediated delivery of the CRISPR/Cas9 system to somatic cells of adult animals. We apply it to generate a mouse model of Eml4-Alk-driven lung cancer. The resulting tumours invariably harbour the Eml4-Alk inversion, express the Eml4-Alk fusion gene, display histopathological and molecular features typical of ALK(+) human NSCLCs, and respond to treatment with ALK inhibitors. The general strategy described here substantially expands our ability to model human cancers in mice and potentially in other organisms.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nature13902

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 30 references

Cited by

Sorted by citations

Items 201–300 of 633

Metadata

Authors
Maddalo, D., Manchado, E., Concepcion, C. P., Bonetti, C., Vidigal, J. A., Han, Y.-C., Ogrodowski, P., Crippa, A., Rekhtman, N., de Stanchina, E., Lowe, S. W., & Ventura, A.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Azienda Ospedaliera San Gerardo (IT)
Corresponding author
Ventura, Andrea
Venue
Nature
Published
2014-10-22
Volume
516
Issue
7531
Pages
423-427
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1972759536
Cited by
640
References
30
Citations by year
2026: 21 · 2025: 29 · 2024: 43 · 2023: 45 · 2022: 61 · 2021: 53 · 2020: 53 · 2019: 55 · 2018: 68 · 2017: 65 · 2016: 81 · 2015: 63 · 2014: 2
FWCI
28.86
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Memorial Sloan-Kettering Cancer Center
  • National Institutes of Health
  • National Cancer Institute (P01CA129243, P01CA013106, P30CA008748)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
EML4-ALK fusion, chromosomal rearrangements, non-small cell lung cancer, somatic genome editing, tumor suppressor, oncogene cooperation
MeSH terms
Crizotinib, Anaplastic Lymphoma Kinase, Animals, Antineoplastic Agents, Cells, Cultured, Disease Models, Animal, Genetic Engineering, Chromosome Inversion, Lung Neoplasms, Pyrazoles, Pyridines, Translocation, Genetic, Receptor Protein-Tyrosine Kinases, NIH 3T3 Cells, Protein Kinase Inhibitors, Mice, Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-Cas Systems, CRISPR-Associated Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review