Somatic Engineering of Oncogenic Chromosomal Rearrangements: A Perspective

Abstract

The ability to engineer specific mutations in mice has proven essential to advancing our understanding of the molecular basis of cancer. Chromosomal rearrangements, a common and clinically relevant class of cancer-causing mutations, have however remained difficult to faithfully recapitulate in vivo The development of genetic tools for in vivo somatic genome editing has recently overcome this limitation and led to the generation of more sophisticated and accurate preclinical models of human cancers. Here, we review the potential applications of these new technologies to the study of tumor biology and discuss their advantages over more conventional strategies, their limitations, and the remaining challenges. Cancer Res; 76(17); 4918-23. ©2016 AACR.

Figure 1. Modeling oncogenic chromosomal rearrangements by genome editing

Schematic representation of the possible chromosomal rearrangements generated upon introduction of two concomitant double stranded breaks. Only stable rearrangements are shown for simplicity, but dicentric and acentric chromosomes will also be generated in the process. For each type of rearrangement, a representative example of a corresponding oncogenic gene fusion found in human cancers is also shown.