Molecular Profiling of Clinical Specimens

临床分子分析核心（CMPC）是一个协作核心，旨在超越其他实验室核心的通用服务范式。其人员的专业知识允许从项目开始（如方案制定）到检测和生物统计分析的执行。目前，我们的主要职能是支持国家癌症研究所（NCI）的临床试验，为此，我们与癌症研究中心（CCR/NCI）的许多分支机构和NCI的姐妹中心合作。这些合作的状态包括从初步讨论到方案制定、累积和分析、完成到发表；对于那些已经完成的，我们期待参与后续研究。许多研究是临床试验，测试或确定早期临床试验的药物。这些研究包括：“CaboNivo或cabonvoip治疗转移性尿路上皮癌和泌尿生殖系统癌的一期研究”以及与NCI/CCR GIST诊所的相互作用。在过去，我们支持了“晚期胸腔恶性肿瘤的分子分析和靶向治疗：生物标志物衍生的多组多组织学II期筐试验”和“弥漫性内在脑桥胶质瘤的功能定义治疗靶点”的试验，以及最近Shukla等人的“使用诱导多能干细胞模型识别肺癌治疗的新靶点”，2018。然而，其他研究更侧重于了解特定疾病的潜在病理，而不是直接测试一种治疗方法。这些研究包括Oltmann等人发表的《非整倍体、TP53突变和MYC扩增与乳腺癌患者肿瘤内异质性增加和预后不良相关》和Hirsh等人发表的《克罗恩病相关结直肠癌发生的基因组改变动力学》。值得注意的是，在CLIA（临床实验室改进修订）实验室的背景下，资源已经投入到使用Illumina下一代测序来实现临床外显子组和多基因面板高深度测序。为了支持这些研究，CMPC在许多分子技术方面拥有专业知识，用于分析人类标本的DNA和RNA。在CMPC中使用的其他最先进的分析是广泛的先进平台，包括：RNA-seq， mRNA表达分析（微阵列，实时PCR，基于珠状细胞），表观基因组甲基化（微阵列），阵列比较基因组杂交（微阵列）和端粒长度分析。重要的是，CMPC为所有这些检测提供了完整的生物信息学支持。

The Clinical Molecular Profiling Core (CMPC) is a collaborative core that seeks to go beyond the common service paradigm of other laboratory cores. The expertise of its personnel allows involvement from the start of a project, such as the protocol development, through performance of the assay and biostatistical analyses. Currently, our main function is to support clinical trials at the National Cancer Institute (NCI) and to that end we have collaborations with many of the branches in the Center for Cancer Research (CCR/NCI) and sister centers in the NCI. The status of these collaborations range from preliminary discussions through protocol development, accrual and analysis, and completion to publication; for those that are completed, we look forward to being involved in follow up studies. Many of the studies are clinical trials testing or identifying drugs for early phase clinical trials. These include studies such as: "Phase 1 study of CaboNivo or CaboNivoIp in Metastatic Urothelial and Genitourinary Cancer" and interactions with the NCI/CCR GIST Clinic. In the past we have supported "Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial" and a trial in "Functionally defined therapeutic targets in diffuse intrinsic pontine glioma" and recently Shukla et al., Identification of Novel Targets for Lung Cancer Therapy Using an Induced Pluripotent Stem Cell Model, 2018. However, other investigations are more focused on understanding the underlying pathology of specific diseases and are not directly testing a therapy. These studies included publications by Oltmann et al., Aneuploidy, TP53 mutation, and amplification of MYC correlate with increased intratumor heterogeneity and poor prognosis of breast cancer patients and Hirsh, et al., Dynamics of genome alterations in Crohn's disease associated colorectal carcinogenesis. Significantly, resources have been devoted to actualizing clinical exome and multi-gene panel hi-depth sequencing using Illumina next-generation sequencing in the context of our CLIA [Clinical Laboratory Improvement Amendments] laboratory. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA and RNA from human specimens. Other state of the art assays utilized in the CMPC are a wide range of advanced platforms that include: RNA-seq, mRNA expression analysis (microarray, real-time PCR, bead-based), epigenomic methylation (microarray), array comparative genomic hybridization (microarray), and telomere length assays. Importantly, the CMPC provides full bioinformatics support for all these assays.