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Chromosome Translocation pp 15–25Cite as

Induction of Chromosomal Translocations with CRISPR-Cas9 and Other Nucleases: Understanding the Repair Mechanisms That Give Rise to Translocations

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1044))

Abstract

Chromosomal translocations are associated with several tumor types, including hematopoietic malignancies, sarcomas, and solid tumors of epithelial origin, due to their activation of a proto-oncogene or generation of a novel fusion protein with oncogenic potential. In many cases, the availability of suitable human models has been lacking because of the difficulty in recapitulating precise expression of the fusion protein or other reasons. Further, understanding how translocations form mechanistically has been a goal, as it may suggest ways to prevent their occurrence. Chromosomal translocations arise when DNA ends from double-strand breaks (DSBs) on two heterologous chromosomes are improperly joined. This review provides a summary of DSB repair mechanisms and their contribution to translocation formation, the various programmable nuclease platforms that have been used to generate translocations, and the successes that have been achieved in this area.

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Acknowledgments

MSK research is supported by NIH/NCI Cancer Center support grant P30 CA008748. This work was supported in part by an Alex’s Lemonade Stand Innovation Award and NIH R01CA185660 and R35GM118175 (M.J.). E.B. research is supported by ANR-12-JSV6-0005, the Canceropole IdF, the Institut National du Cancer and la Ligue Contre le Cancer (Equipe de Villartay, Labelisée La Ligue Contre Le Cancer).

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Authors and Affiliations

  1. Genome Dynamics in the Immune System Laboratory, Institut Imagine, INSERM UMR 1163, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    Erika Brunet

  2. Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Maria Jasin

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  1. Erika Brunet
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  2. Maria Jasin
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Correspondence to Erika Brunet or Maria Jasin .

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  1. National Institute of Biological Sciences, Beijing, China

    Yu Zhang

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Brunet, E., Jasin, M. (2018). Induction of Chromosomal Translocations with CRISPR-Cas9 and Other Nucleases: Understanding the Repair Mechanisms That Give Rise to Translocations. In: Zhang, Y. (eds) Chromosome Translocation. Advances in Experimental Medicine and Biology, vol 1044. Springer, Singapore. https://doi.org/10.1007/978-981-13-0593-1_2

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