Figure 4.
Proposed model of retrograde glandular colonization. All invasive adenocarcinoma cells are ERG-positive due to an early TMPRSS2–ERG fusion event, yet only part of the invasive adenocarcinoma shows PTEN loss and is therefore considered subclonal loss. In such an ERG-positive invasive adenocarcinoma with subclonal loss of PTEN, TMPRSS2–ERG genomic breakpoint analysis establishes the shared clonal origin of lesions. Subclonal PTEN loss can be used as a temporal vector. The observation that ERG-positive PTEN-negative cells populate normal acinar and ductal structures strongly suggests a retrograde spreading pattern of invasive carcinoma cells into benign glandular structures. PTEN-proficient normal prostate epithelial cells and adenocarcinoma are shown in brown. PTEN-deficient cells are drawn in grey. ERG overexpression is indicated by blue nuclei. Intact basal cells are highlighted in red.
