The evaluation of fusion gene incidance in prostate cancer and its clinical relationship
Project no. 20263 · Status: Kapanmış (Yayın bekleniyor) · 2018
Summary
Prostate cancer is a common disease associated with high mortality and morbidity which is the leading cause of cancer death in men worldwide. Despite efforts to profile prostate cancer at transcriptional and proteomic levels, potential genetic alterations associated with disease progression and molecular biological signaling pathways underlying the disease have still not been identified. Recent studies have shown that gene fusions are significantly effective in the development of prostate cancer. ERG is an oncogene that can fuse with TMPRSS2 to form an oncogenic fusion gene (TMPRSS2-ERG) in prostate cancer, often found in hormone resistant patients. The fusion gene resulting in ERG overexpression affects androgen receptor expression, leading to prostate cancer progression. In our study, we collected tumor tissue and urine samples of 58 cases diagnosed with prostate cancer in the project and developed an RT-PCR array method specific to the detection of 12 fusion genes, which are the most common fusion genes in prostate cancer, including C15ORF217-ETV1, CANT1-ETV4, DDX5-ETV4, FLJ35294-ETV1, HERV-ETV1, HNRPA2B1-ETV1, SLC45A3-ETV1, SLC45A3-ETV5, TMPRSS2-ERG, TMPRSS2-ETV1, TMPRSS2-ETV4 and TMPRSS2-ETV5. We confirmed our results with agarose gel electrophoresis. Although the most common fusion in prostate cancer in the literature was TMPRSS2-ERG, the most common gene fusion in our study was HNRPA2B1-ETV1 with a rate of 46.5 % in urine samples (n=58) and 24.5 % in tissue samples (n=53), and it could be detected with higher sensitivity in the urine samples compared to the tissues. In addition, TMPRSS2-ERG, SLC45A3-ETV5, SLC45A3-ETV1, FLJ35294-ETV1 and DDX-ETV4 gene fusions were also detected in the tissue and urine samples of other cases. In conclusion, we showed that the rapid RT-PCR array method we developed for simultaneous determination of 12 different gene fusions can be used in diagnosis and follow-up of prostate cancer, and that more sensitive results are obtained especially from urine samples that can be collected non-invasively.