Abstract 2347: PSA splice variants and their expression in prostate cancer

Introduction Prostate cancer (PCa) is the second most common cancer in American men, resulting in 32,000 deaths annually. Challenges for the management of PCa include the inability to distinguish indolent from aggressive and untreatable castration-resistant PCa. These challenges can be addressed by understanding the molecular basis of cancer initiation and progression. Prostate specific antigen (PSA) is widely used for screening, diagnosing and monitoring of PCa, although it is also elevated in other disorders and therefore lacks specificity and sensitivity. Alternative splicing is a common mechanism used in nature to enhance protein diversity. Alternative splicing of the PSA gene produces at least 15 transcripts of 0.7-6.1 kb (Heuzé-Vourc'h et al 2003). Several variants of PSA have been reported and are shown to be differentially expressed in PCa compared to normal prostates or to benign prostatic hyperplasia (BPH). Here we describe the identification of four variants of PSA with the potential to improve on the specificity of the PSA test. Material and Methods Human prostate cDNAs were from cryopreserved prostate tissues collected after radical prostatectomies and have been described previously (Mubiru et al. 2004). PCR was carried out using primers that amplify the complete PSA mRNA and also those specific for the most common splice variant (Heuzé-Vourc'h et al. 2001). The PCR products were inserted into the PCR2.1-TOPO vector (Life Technologies) and sequenced. Results We identified four novel splice variants of the PSA gene. Novel PSA Splice VariantsTypeNameContaining Exons (Ex) and Introns (In)Molecular Weight (Da)pIPSA mRNAPSAEx3del246Ex1, Ex2, Partial Ex38,5949.61PSA mRNAPSA25RVEx1, Partial In111,1815.55PSA mRNAPSA Yang 28Ex1, Ex2, Ex514,1539.59PSA mRNAPSA Yang 21Ex1, Ex2, Partial Ex3, Ex4, Ex523,6986.64 Results also indicate that some transcripts are differentially expressed in tumors compared to non-tumors. References 1.Mubiru JN, et al. (2004). Gene 327: 89-98. 2.Heuzé-Vourc'h N, et al. (2003) Eur J Biochem 270: 706-714. 3.Heuzé-Vourc'h N, et al. (2001) Eur J Biochem 268: 4408-4413. Citation Format: Alice S. Yang, Thushari Alahapperuma, James N. Mubiru, Magdalena Garcia-Forey, Robert E. Shade. PSA splice variants and their expression in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract