Evidence map›Paper›PMID 25337876›Full record

ArticleNature2014

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

Danilo Maddalo, Eusebio Manchado, Carla P Concepcion, Ciro Bonetti, Joana A Vidigal, Yoon-Chi Han, Paul Ogrodowski, Alessandra Crippa, Natasha Rekhtman, Elisa de Stanchina and 2 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature, 2014. 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 375 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
375citing papers in PubMed, 1 pooled it
30.9field-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

375 citing papers in PubMed, 1 synthesis or guideline pooled it, 653 citations in OpenAlex.

  1. Pooled it
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  6. ALK Knock-In Reporter Reveals APE1 as a Negative Regulator ofInternational journal of molecular sciences · 2026
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  11. Improved vector toolkit for genome writing in mammalian cells.bioRxiv : the preprint server for biology · 2026
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315 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Danilo MaddaloMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Eusebio ManchadoMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Carla P Concepcion1] Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA [2] Weill Cornell Graduate School of Medical Sciences of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Ciro BonettiMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Joana A VidigalMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Yoon-Chi HanMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Paul OgrodowskiMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Alessandra CrippaMilano-Bicocca University, Department of Medical Oncology, San Gerardo Hospital, 20052, Via G B Pergolesi 33, Monza, Italy.
Natasha RekhtmanMemorial Sloan Kettering Cancer Center, Thoracic Pathology and Cytopathology, 1275 York Avenue, New York, New York 10065, USA.
Elisa de StanchinaMemorial Sloan Kettering Cancer Center, Molecular Pharmacology Program, 1275 York Avenue, New York, New York 10065, USA.
Scott W Lowe1] Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA [2] Howard Hughes Medical Institute, 1275 York Avenue, New York, New York 10065, USA.
Andrea VenturaMemorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA.
Memorial Sloan Kettering Cancer Center · USHoward Hughes Medical Institute · USUniversity of Milano-Bicocca · IT

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
VIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI William Richard McCombie · 1985 to 2026
$116.8M
The Role of Focal Oncogene Amplifications in Lung CancerP01CA129243 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Piro Lito · 2007 to 2026
$31.2M
Howard Hughes Medical InstituteNCI NIH HHS P01 CA013106NCI NIH HHS P01 CA129243NCI NIH HHS P30 CA008748
6 · The paper itself

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.

Indexed as

CRISPR-Cas SystemsAnaplastic Lymphoma KinaseAnimalsAntineoplastic AgentsCells, CulturedChromosome InversionClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCrizotinibDisease Models, AnimalGenetic EngineeringLung NeoplasmsMiceNIH 3T3 CellsProtein Kinase InhibitorsPyrazolesALK protein, humanAlk protein, mouseAnaplastic Lymphoma KinaseAntineoplastic AgentsCRISPR-Associated ProteinsCrizotinibProtein Kinase InhibitorsPyrazolesPyridinesReceptor Protein-Tyrosine Kinases

Identifiers

PMID25337876
PMCPMC4270925
OpenAlexW1972759536

What OpenQuestion holds

Textmetadata
LicenceTDM
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.