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We previously demonstrated that the <i>Trp53-R270H</i> mutation can drive prostate cancer (CaP) initiation using the FVB.129S4 (Trp53^tm3Tyj/wt); FVB.129S (Nkx3-1^{tm3(cre)Mmswt}) genetically engineered mouse model (GEM). We now validate this finding in a different model (B6.129S4-<i>Trp53</i>^tm3.1Tyj/J mice) and use RNA-sequencing (RNA-Seq) to identify genes which may contribute to <i>Trp53 R270H</i>-mediated prostate carcinogenesis. Wildtype (<i>Trp53^WT/WT</i>), heterozygous (<i>Trp53^R270H/WT</i>), and homozygous mice (<i>Trp53^R270H/R270H</i>) were exposed to 5 Gy irradiation to activate and stabilize p53, and thereby enhance our ability to identify differences in transcriptional activity between the three groups of mice. Mouse prostates were harvested 6 h post-irradiation and processed for histological/immunohistochemistry (IHC) analysis or were snap-frozen for RNA extraction and transcriptome profiling. IHC analyses determined that presence of the <i>Trp53-R270H</i> mutation impacts apoptosis (lower caspase 3 activity) but not cell proliferation (Ki67). RNA-Seq analysis identified 1378 differentially expressed genes, including wildtype p53 target genes (E.g., <i>Cdkn1a</i>, <i>Bax</i>, <i>Bcl2</i>, <i>Kras</i>, <i>Mdm2</i>), p53 gain-of-function (GOF)-related genes (<i>Mgmt, Id4</i>), and CaP-related genes (<i>Cav-1, Raf1, Kras</i>). Further understanding the mechanisms which contribute to prostate carcinogenesis could allow for the development of improved preventive methods, diagnostics, and treatments for CaP.