In order to provide a framework that enables the development of effective therapies, the aggressive variant prostate cancers (AVPCs) have been defined as a subset of the disease with atypical and virulent clinicopathological features frequently associated with androgen-indifferent tumors (AVPC clinicopathological, AVPC-c) [1], which are also characterized by a molecular profile of combined defects in any two or more of the three tumor suppressors (TSPs) TP53, RB1 and PTEN (AVPC molecular, AVPC-m) [2]. The gene discussed is PTEN; the disease is prostate cancer.