Taken together, these results demonstrate that the frequencies and patterns of alteration affecting KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex components are tumor-type and tissue specific and that, in OVCA, copy-number loss affecting RBX1 is the most prominent mechanism likely contributing to the increased NRF2 activation observed in ovarian cancer. Here, KEAP1 is linked to ovarian cancer.