Selected Articles from This Issue

African American men are particularly susceptible to prostate cancer incidence, but genetic factors mediating prostate cancer risk in African American men remain poorly defined. To search for genetic contributors to prostate cancer occurrence in African American men, Zhang and colleagues performed whole exome sequencing using blood samples from men from 20 families affected by hereditary prostate cancer. Sequencing revealed a rare non-synonymous ADPRHL1 variant, c.A233T, encoding a p.D78V amino acid conversion, that was present in men affected by prostate cancer in four of the families but not present in 170 unrelated healthy African American men. Functional studies demonstrated that the A233T variant increases prostate cancer cell growth and induces PARP activation. A233T variant-mediated PARP activation renders prostate cancer cells resistant to DNA damaging agents but susceptible to PARP inhibitor olaparib. The authors also found that ADPRHL1 abundance decreases during prostate cancer progression, suggesting A233T is a loss-of-function variant. Altogether, this...