The Use of Innovative Tools to Reproduce Human Cancer Translocations: Lessons from the CRISPR/Cas System
Juan C. Ramirez.
The development of cancer is associated with alterations to the physiology
of the cell caused by multiple changes in its genome. A frequent genomic event in
cancer is chromosome translocation, an exchange of large DNA fragments between
two non-homologous chromosomes that in many cases leads to the creation of new fusion genes.
Chromosome translocations are key events in the initiation or progression of many neoplastic processes. The difficulty in
generating specific chromosome translocations in the laboratory has meant that researchers have lacked appropriate
cellular models in which to investigate the effect of these key cancer markers. Different genome-engineering strategies
used to induce defined chromosome translocations have met with varying success. Recently, the use of the RGEN
technology (RNA-guided endonuclease), also known as the CRISPR/Cas9 system, has demonstrated as proof-of-principle
that it is possible to engineer cells to undergo these specific chromosomal translocations with high efficiency. Using this
advance, it is now possible to easily and accurately generate cell models harboring the same alterations that define tumor
cells from patients, allowing researchers to experimentally recapitulate the genomic alterations needed to transform a
healthy cell. In this review, we summarize the different methods used to mimic cancer-related chromosomal translocations
and highlight the advantages of RGEN technology for improving the generation of models for the study of cancer. These
advances will in time lead to the development of better therapeutic approaches to the treatment of cancer.
Keywords: Acute myeloid leukemia, cancer model, chromosome translocation, CRISPR/Cas9, Ewing’s sarcoma, gene editing.
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