SubclonalCHD1deletion is more frequent in African American prostate cancers and associated with rapid disease progression and limited levels of homologous recombination deficiency

Chromodomain helicase DNA-binding protein 1 ( CHD1 ) is frequently deleted in a subset of prostate cancers. We show here that subclonal deletion of CHD1 is nearly three times as frequent in prostate tumors of African American men than in men of European ancestry and it associates with rapid disease progression. We further show that CHD1 deletion is associated with only one type of the homologous recombination deficiency associated mutational signatures in prostate cancer. In prostate cancer cell line models CHD1 deletion did not induce HRD as detected by RAD51 foci formation assay, which was consistent with the moderate increase of olaparib sensitivity. CHD1 deficient prostate cancer cells, however, still showed markedly increased sensitivity to talazoparib, which could be effective for the treatment of CHD1 deficient tumors in the context of hormone therapy resistant prostate cancer.