Abstract:
:Gene editing techniques have been extensively used to attempt to model recurrent genomic rearrangements found in tumor cells. These methods involve the induction of double-strand breaks at endogenous loci followed by the identification of breakpoint junctions within a population, which typically arise by nonhomologous end joining. The low frequency of these events, however, has hindered the cloning of cells with the desired rearrangement before oncogenic transformation. Here we present a strategy combining CRISPR-Cas9 technology and homology-directed repair to allow for the selection of human mesenchymal stem cells harboring the oncogenic translocation EWSR1-WT1 found in the aggressive desmoplastic small round cell tumor. The expression of the fusion transcript is under the control of the endogenous EWSR1 promoter and, importantly, can be conditionally expressed using Cre recombinase. This method is easily adapted to generate any cancer-relevant rearrangement.
journal_name
Proc Natl Acad Sci U S Aauthors
Vanoli F,Tomishima M,Feng W,Lamribet K,Babin L,Brunet E,Jasin Mdoi
10.1073/pnas.1700622114subject
Has Abstractpub_date
2017-04-04 00:00:00pages
3696-3701issue
14eissn
0027-8424issn
1091-6490pii
1700622114journal_volume
114pub_type
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