In agreement with the observation that the elevated BRD4 level and the downstream signaling are critical for JQ1 resistance in PCa cells harboring SPOP hotspot mutants such as F133V and W131R (Zhang et al, 2017), the protein levels of BRD4 and phosphorylated AKT were lower in Q165P mutant cells compared to F133V expressing cells, organoids, and PDX tumors (Figs 2C and D and 6A). Here, BRD4 is linked to posterior cortical atrophy.