Alex Kentsis and colleagues identify somatic genomic rearrangements in primary human rhabdoid tumors characterized by deletions and inversions involving PGBD5-specific signal sequences at their breakpoints. They further show that ectopic expression of PGBD5 in primary immortalized human cells is sufficient to promote cell transformation in vitro and in immunodeficient mice in vivo, thus defining PGBD5 as an oncogenic mutator and providing a plausible mechanism for site-specific DNA rearrangements in solid tumors.
- Anton G Henssen
- Richard Koche
- Alex Kentsis
