Molecuar Sub-typing of Prostate Cancer Based on Recurrent Gene Fusions

描述(申请人提供)：使用生物信息学方法分析前列腺癌基因表达谱，我们确定了大多数前列腺癌的复发基因融合/易位(Tomlins等人，科学2005)。具体地说，我们鉴定了TMPRSS2的雄激素调节元件与ETS转录因子家族的成员融合，包括ERG、ETV1、ETV4和ETV5。与血液系统恶性肿瘤类似，前列腺癌中发现的基因融合/易位可能代表疾病的病因学生物标志物和分子亚型。在这项应用中，我们计划集中我们的努力来表征这类新的基因融合生物标记物。我们小组和其他人所做的初步工作表明，基因融合的分子亚型和转录变体可能与前列腺癌的临床亚型有关。这一应用的中心假设是，基于基因融合和变异的分子亚型将是临床上局部前列腺癌侵袭性潜力的有用预测指标，从而指导治疗。鉴于此，我们提出了以下目标：特定目标1：发现和提名前列腺癌新的分子亚型。具体目标2：在根治性前列腺切除术队列中，确定前列腺癌的分子亚型与临床结果和/或疾病侵袭性的关系。具体目标3：使用前列腺活检样本来表征前列腺癌的分子亚型与临床结果和/或疾病侵袭性的关系。

DESCRIPTION (provided by applicant): 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.