Integrative molecular imaging and sequencing of prostate cancer

描述（由申请人提供）：局限性前列腺的诊断传统上是通过经直肠超声（TRUS）引导活检进行的，发现患有局限性器官局限性前列腺癌的男性通常通过手术切除前列腺、放射治疗或主动监测进行管理。直到最近，前列腺成像和肿瘤评估的局限性极大地限制了我们准确评估与个体局限性前列腺癌相关的遗传和代谢异常以指导后续临床管理的能力。此外，了解前列腺癌的遗传和代谢基础有可能为开发这种疾病的有效治疗形式提供基础。本申请试图将NIH开发的前列腺癌的先进MRI和代谢成像与密歇根转化病理学中心（MCTP）采用的综合临床测序方法“结合”。鉴于此，目的如下：目的1，在NIH MRI/代谢成像项目中招募已知或疑似前列腺癌的患者。目的2、对60例经冰冻切片确诊的临床局限性前列腺癌患者进行全外显子组和转录组测序分析 目标1中获得的活检材料。我们将进行整合测序，包括肿瘤/正常的全外显子组测序，以及配对末端转录组和外显子组捕获转录组测序。通过进行这些分析，我们提出，我们将捕获患者肿瘤中可能存在的可操作和信息突变的“宇宙”。这些突变包括体细胞核酸取代、小插入缺失、基因融合/易位、扩增/缺失和异常基因表达。目的3、综合分析本临床试验活检组织的组织病理学、分子影像学、代谢、突变景观和基因表达改变。活检将进行病理分析以及全面的分子分析，以便与匹配的多参数MRI，C13超极化成像和病理学相关联，其预期目标是确定惰性与侵袭性癌症的遗传基础。

DESCRIPTION (provided by applicant): The diagnosis of localized prostate has traditionally been performed with transrectal ultrasound (TRUS) guided biopsy and men found to have localized, organ-confined prostate cancer are conventionally managed with surgical removal of the prostate, radiation therapy or active surveillance. Until recently, limitations of prostate imaging and tumor assessment have greatly limited our ability to accurately assess the genetic and metabolic abnormalities associated with an individual's localized prostate cancer in order to guide subsequent clinical management. In addition, understanding the genetic and metabolic basis of prostate cancer has the potential to provide the foundation for the development of effective forms of therapy for this disease. This application attempts "to marry" the advanced MRI and metabolic imaging of prostate cancer developed at the NIH with the integrative clinical sequencing approaches employed by the Michigan Center for Translational Pathology (MCTP). Given this the Aims are as follows: Aim 1, Enroll patients with known or suspicious for prostate cancer in the NIH MRI/metabolic imaging program. Aim 2, Whole exome and transcriptome sequencing analysis of 60 patients identified with clinically localized prostate cancer from frozen biopsy material obtained in Aim 1. We will carry out integrative sequencing that involves whole exome sequencing of the tumor/normal, and paired-end transcriptome and exome-capture transcriptome sequencing. By carrying out these analyses, we propose that we would be capturing the "universe" of actionable and informative mutations a patient might harbor in their tumor. These mutations include somatic nucleic acid substitutions, small indels, gene fusions/translocations, amplifications/deletions, and outlier gene expression. Aim 3, Integrative analysis of histopathology, molecular imaging, metabolism, mutational landscape and gene expression alterations of biopsy material from this clinical trial. The biopsies will undergo pathologic analysis as well as comprehensive molecular profiling in order to make associations with matched multiparametric MRI, C13 hyperpolarized imaging and pathology with the intended goal of determining the genetic basis of indolent versus aggressive cancers.