Employing a bioinformatics approach to analyze prostate cancer gene expression profiles, we identified recurrent gene fusions/translocations in the majority of prostate cancers (Tomlins et al, Science 2005). Specifically, we identified the androgen regulatory elements of TMPRSS2 fused to the members of the ETS family of transcription factors including ERG, ETV1, ETV4 and ETV5. Analogous to hematological malignancies, gene fusions/translocations identified in prostate cancer may represent pathognomonic biomarkers and molecular sub-types of disease. In this application, we plan to focus our efforts on characterizing this new class of gene fusion biomarkers. Preliminary work done by our group and others suggest that molecular subtypes as well as transcript variants of gene fusions may be associated with clinical sub-types of prostate cancer. The central hypothesis of this application is that molecular sub-types based on gene fusions and variants will be useful predictors of the aggressive potential of clinically localized prostate cancer and thus guide treatment. Given this, we propose the following Aims:
Specific Aim 1 : Discovery and nomination of novel molecular sub-types of prostate cancer.
Specific Aim 2 : Characterize associations of molecular sub-types of prostate cancer with clinical outcome and/or aggressiveness of disease in a radical prostatectomy cohort.
Specific Aim 3. Characterize associations of molecular sub-types of prostate cancer with clinical outcome and/or aggressiveness of disease using prostate needle biopsy samples.
Project Narrative: The discovery of genes fused together is a major advancement in the understanding of prostate cancer. This proposal is about using these """"""""gene fusions"""""""" to identify prognostic categories to improve approaches to the treatment of prostate cancer patients.
|Tomlins, Scott A; Day, John R; Lonigro, Robert J et al. (2016) Urine TMPRSS2:ERG Plus PCA3 for Individualized Prostate Cancer Risk Assessment. Eur Urol 70:45-53|
|Mani, Ram S; Amin, Mohammad A; Li, Xiangyi et al. (2016) Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer. Cell Rep 17:2620-2631|
|Qiao, Yuanyuan; Feng, Felix Y; Wang, Yugang et al. (2016) Mechanistic Support for Combined MET and AR Blockade in Castration-Resistant Prostate Cancer. Neoplasia 18:1-9|
|Niknafs, Yashar S; Han, Sumin; Ma, Teng et al. (2016) The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. Nat Commun 7:12791|
|Sahu, Anirban; Singhal, Udit; Chinnaiyan, Arul M (2015) Long noncoding RNAs in cancer: from function to translation. Trends Cancer 1:93-109|
|Iyer, Matthew K; Niknafs, Yashar S; Malik, Rohit et al. (2015) The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 47:199-208|
|Kumar-Sinha, Chandan; Kalyana-Sundaram, Shanker; Chinnaiyan, Arul M (2015) Landscape of gene fusions in epithelial cancers: seq and ye shall find. Genome Med 7:129|
|Wei, John T (2015) Urinary biomarkers for prostate cancer. Curr Opin Urol 25:77-82|
|Prensner, John R; Zhao, Shuang; Erho, Nicholas et al. (2014) RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncol 15:1469-80|
|Prensner, John R; Chen, Wei; Han, Sumin et al. (2014) The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc. Neoplasia 16:900-8|
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