Rebellious enzymes: mutation showers in cancer induced by APOBEC ‘kataegisters’

In 2012, cancer genomics saw the addition of a new phrase to its lexicon: kataegis, Greek for thunderstorm and an apt description for the discovery of localized regions of hypermutation that were revealed when numerous breast cancer genomes were sequenced in a landmark study in Cell. Michael Stratton from the Wellcome Trust Sanger Institute, UK, and fellow co-authors of the study speculated that the APOBEC family of enzymes could be responsible. The first attempt to test this theory was led by Youri Pavlov and Artem Lada from the University of Nebraska Medical Center, USA, and colleagues, who demonstrated that the APOBEC PmCDA1 could indeed cause kataegis in a yeast model, as published in a Biology Direct study. Here, Pavlov and Lada discuss how this story unfolded, explaining why APOBECs became the prime suspect in the case of kataegis.