Chronic androgen deprivation therapy increased of about four fold the proportion of AR-/NE- CRPCs: this subgroup of prostate cancers retained AR amplification, TP53 mutations and PTEN loss like AR+/NE- cancers, thus suggesting that differences in recurrent genetic alterations cannot explain the biologic differences between these two prostate cancer subgroups (Figure 4) [215]. Here, PTEN is linked to Familial prostate cancer.