Publication: TOP2B binding delineates mutational processes and driver mutations
The Reimand lab published “Topoisomerase IIb binding delineates localized mutational processes and driver mutations in cancer genomes” in Nature Communications. The study was co-led by Drs. Liis Uusküla-Reimand (SickKids) and Christian Lee (OICR, Reimand lab), with major contributions from the labs of Drs. Michael Wilson (SickKids), Daniel Schramek (LTRI) and Mamatha Bhat (UHN).
The team uncovered how TOP2B, an enzyme that relieves DNA stress and is also an off-target of common chemotherapies, can mark hotspots where cancer-driving mutations arise. By integrating TOP2B binding maps with thousands of tumour genomes, the team identified dozens of previously unrecognised non-coding driver regions, including a highly mutated regulatory element at the RMRP non-coding RNA gene, which they validated experimentally. The work sits at the intersection of mutational processes, genome biology and driver mutations in cancer.