Genomics and Proteomics

高通量基因组生物技术的应用在很大程度上加速了对多发性骨髓瘤（MM）分子异质性的阐明。鉴于基因表达谱（GEP）在350多名患者的总治疗2方案和450多名患者的总治疗3方案中取得了成功，并且需要更好地了解MM的细胞和分子生物学，包括其微环境（ME），以便开发有效靶向肿瘤细胞和ME的治疗方法，我们建议继续并扩大，这项工作适用于所有在项目1中进入临床试验的新诊断患者，以及在项目2中接受新型同种异体自然杀伤细胞疗法的总疗法3、4和5的复发患者。随着蛋白质组学技术的最新进展，我们还将对大多数这些患者的肿瘤细胞进行蛋白质组学分析（PP）。GEP已经并将成为我们在项目3和项目4中研究骨髓ME的MM肿瘤细胞操作的不可或缺的工具。这个基因组学和蛋白质组学核心的主要目标是提供一个高度专业化的分子共享资源，将服务于已建立的研究项目。该资源结合了骨髓瘤遗传学的Donna D. and Donald M. Lambert实验室和Winthrop P. Rockefeller癌症研究所骨髓瘤研究和治疗研究所骨髓瘤蛋白质组学的Nancy and Stephen Grand实验室的设施和专业知识。具体目标1：通过提供来自体外和体内模型的临床材料和细胞的基因组学和蛋白质组学分析，协助开展每个P01项目的研究。具体来说，GEP和PP将在患者样本、体内动物模型研究样本和体外细胞培养研究样本上进行。特定目标2：维护和关联基因组和蛋白质组学研究的数据。与核心A和项目3的生物统计学组成部分合作，对GEP和PP数据进行数据挖掘和统计分析，将为MM的治疗和风险分层预测模型的发展提供基础。在项目4中，GEP和PP将帮助确定体外模型系统中骨髓瘤细胞与破骨细胞和成骨细胞相互作用中改变的遗传途径。

Utilization of high-throughput genomic biotechnologies to a great extent accelerated the elucidation of the molecular heterogeneity of multiple myeloma (MM). In view of the success of gene expression profiling (GEP) of more than 350 patients on the Total Therapy 2 protocol and more than 450 patients on the Total Therapy 3 protocols who have been studied with this technique¿and the need to better understand the cellular and molecular biology of MM, including its microenvironment (ME), in order to develop treatments that effectively target tumor cells and the ME¿we propose to continue, and expand, this work on all newly diagnosed patients entering clinical trials in Project 1, as well as patients on Total Therapies 3,4, and 5 experiencing relapse who enter salvage trials with novel allogeneic natural killer cell therapies in Project 2. With the recent advances in proteomic technologies, we will also perform proteomic profiling (PP) on tumor cells from the majority of these patients. GEP has been and will be an indispensable tool in our investigation of MM tumor cell manipulation of the bone marrow ME in Project 3 and Project 4. The primary objective of this Genomics and Proteomics Core is to provide a highly specialized, molecular shared resource that will serve established research projects. This resource combines the facilities and expertise of the Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics and the Nancy and Stephen Grand Laboratory for Myeloma Proteomics at the Myeloma Institute for Research and Therapy of the Winthrop P. Rockefeller Cancer Institute. The objective of this Core will be achieved through the following specific aims: Specific Aim 1: Assist in the conduct of research of each P01 project by providing genomic and proteomic profiling of clinical material and cells derived from in vitro and in vivo models. Specifically, GEP and PP will be performed on patient samples and on samples from in vivo animal model studies and in vitro cell culture studies. Specific Aim 2: Maintain and correlate data from the genomic and proteomic studies. Data mining and statistical analyses of GEP and PP data in collaboration with the biostatistical components of Core A and Project 3 will provide the basis for the development of predictive models for treatment and risk stratification of MM. In Project 4, GEP and PP will help identify genetic pathways altered in the interaction between myeloma cells and osteoclasts and osteoblasts in in vitro model systems.