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, Scott W. Lowe and Andrea Ventura ()
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Danilo Maddalo: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Eusebio Manchado: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Carla P. Concepcion: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Ciro Bonetti: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Joana A. Vidigal: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Yoon-Chi Han: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Paul Ogrodowski: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Alessandra Crippa: Milano-Bicocca University, San Gerardo Hospital, 20052, Via G B Pergolesi 33, Monza, Italy
Natasha Rekhtman: Memorial Sloan Kettering Cancer Center, Thoracic Pathology and Cytopathology, 1275 York Avenue, New York, New York 10065, USA
Elisa de Stanchina: Memorial Sloan Kettering Cancer Center, Molecular Pharmacology Program, 1275 York Avenue, New York, New York 10065, USA
Scott W. Lowe: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA
Andrea Ventura: Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, 1275 York Avenue, New York, New York 10065, USA

Nature, 2014, vol. 516, issue 7531, 423-427

Abstract: The CRISPR/Cas system has been used to induce the Eml4–Alk chromosomal inversion in mice, a characteristic chromosomal rearrangement seen in human non-small cell lung cancers; the mice developed lung cancer and responded to the ALK inhibitor crizotinib, which is used to treat lung cancer patients with the EML4–ALK rearrangement; this general strategy can be used to engineer other disease-associated chromosomal rearrangements in mice and potentially in other organisms.

Date: 2014
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DOI: 10.1038/nature13902

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