Molecular logic underlying chromosomal translocations, random or non-random?

Chromosomal translocations serve as essential diagnostic markers and therapeutic targets for leukemia, lymphoma, and many types of solid tumors. Understanding the mechanisms of chromosomal translocation generation has remained a central biological question for decades. Rather than representing a random event, recent studies indicate that chromosomal translocation is a non-random event in a spatially regulated, site-specific, and signal-driven manner, reflecting actions involved in transcriptional activation, epigenetic regulation, three-dimensional nuclear architecture, and DNA damage-repair. In this review, we will focus on the progression toward understanding the molecular logic underlying chromosomal translocation events and implications of new strategies for preventing chromosomal translocations.