Abstract

Abstract AEG-1/MTDH/LYRIC was initially identified as a HIV-1-inducible gene in primary human fetal astrocytes. Astrocyte Elevated Gene-1 (AEG-1) is ubiquitously overexpressed in all or most cancers and plays a regulatory role in diverse and multiple processes of carcinogenesis. AEG1 is a multi-functional regulator of normal and abnormal physiology; it contributes to broad-spectrum resistance to various chemotherapeutics; and it was recently proposed as the first potential ‘pan-cancer’ gene However, despite its critical relevance to carcinogenesis, until now genetic polymorphisms for this important gene have not been studied for association with cancer susceptibility. For example, though studies have reported AEG-1 gene expression in animal models and tumor tissues, no studies have been reported in Caucasians on the AEG-1 gene polymorphisms in large samples to establish an association with cancers. We report a PCR-RFLP screening protocol for AEG-1 gene polymorphism which is cost effective, simple and reproducible. This study also shows the strong association of AEG-1 gene with prostate cancer risk and metastasis. DNA and RNA was isolated from 232 normal healthy age matched male Caucasians and 129 prostate cancer patients recruited in the study with an informed consent. AEG-1 gene polymorphism (rs2438211) was screened using PCR-RFLP method. Patients were compared with normal healthy controls and also within patient group comparisons were made between primary and metastasis cases. Genotype analysis was done using IBM SPSS 22 software and gene expression analysis was done using RT2 profiler PCR Array Data analysis version 3.5 (SABIOSCIENCES). A strong association of AEG-1 gene polymorphism with prostate cancer (p<0.0001) was observed. A high frequency of the mutant allele was observed in patients (27%) as compared to normal healthy controls (7.9%).This study also highlights the possible effect of AEG-1 interaction with other genes (p53, BCCIP) contributing to tumorigenesis. Citation Format: Radhika Gade Andavolu, Catherine Stafford, Patrick Herling, Isabella Bianco, Jean-Luc Cardenas, Henry Go, Svetlana Rubakovic, Murthy V. Andavolu. Astrocyte elevated gene-1(AEG-1)as a potential diagnostic/prognostic marker for prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4775.

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