Engineering large-scale chromosomal deletions by CRISPR-Cas9

Thomas F Eleveld, Chaimaa Bakali, Paul P Eijk, Phylicia Stathi, Lianne E Vriend, Pino J Poddighe, and Bauke Ylstra

Nucleic Acids Research, gkab557, doi:10.1093/nar/gkab557

Cancer is a genomic disease, where mutations, translocations and chromosomal copy number aberrations drive tumor formation and progression. Isogenic cell line models to study mutations and translocations have given considerable insight into the biological mechanisms behind these aberrations, which has proven pivotal for the development of effective treatment modalities. However, the biological mechanisms that are driven by copy number changes remain elusive, since techniques to generate dedicated isogenic models have been lacking. Here the authors use the unprecedented genome editing capacity of CRISPR-Cas9 to establish a method to generate isogenic cell line models with large chromosomal deletions by essentially cutting out a large chromosomal region and stimulating correct repair with single stranded DNAs. This method is fast and efficient and will accelerate research on the oncogenicity of chromosomal copy number aberrations in cancer.

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