While the TOP2A defect and ‘flat' genomes might possibility be viewed as inconsistent with one another, it is possible that the TOP2A defect in ARID1A mutant tumours has relatively moderate effects (compared with a profound homologous recombination defect for example) on the structure of the genome as it is normally kept in check by proteins such as ATR. The gene discussed is ATR; the disease is neoplasm.