Fig. 8: Cell lines, where HR pathway perturbation resulted in synergy and viability decrease had mutations entangled to the WNT pathway.

Mutations of cell lines that decreased their viability after artificial perturbations mimicking overexpression and gain-of-function mutations of HR pathway members had a common, intrinsic WNT pathway entanglement. These mutant WNT pathway genes caused the overactivation of the WNT pathway, which is known to be a potential resistance mechanism to PARP inhibition. Gain-of-function mutations appeared in proteins important in activating the WNT pathway, while loss-of-function mutations tended to be appearing in negative regulators of the WNT pathway.