Bioinformatics Core

生物信息学核心 项目摘要 所有形式的不可治愈的浆细胞恶性肿瘤、多发性骨髓瘤(MM)和Waldenstrom‘s 巨球蛋白血症(WM)起源于一种被称为受损性单克隆性丙种球蛋白病的前体疾病 重要性(MGUS)。对MGUS细胞的遗传分析提供了证据，表明它是一种基因先进的 病变与MM几乎无法区分。MGUS转变为MM的风险约为每年1%。 MGUS向MM或WM转化的机制尚不清楚。一种可能性是 癌前细胞改变骨髓微环境和/或免疫系统以促进转化 到明显的恶毒。生物信息学核心将从光谱中提供对组织的深入基因组分析 包括无价的纯化肿瘤细胞和整个骨髓的系列样本 MGUS患者的活组织检查登记在观察性临床试验中，并在过去20年中进行了跟踪。 核心还将分析从癌症研究项目1和2获得的实验样本 旨在了解和治疗MGUS进展的预防-拦截(CAP-MGUS中心) 癌前浆细胞、免疫系统和微环境的改变，以消除和/或 延缓恶变的发生。阿肯色大学医学骨髓瘤中心 科学(UAMS)是实验室和临床研究的独特资源，将作为核心的所在地 在研究这些疾病的生物学方面有着悠久的历史。生物信息学的核心 将在大型临床和分子注释档案的背景下使用创新的生物信息学技术 以确定与良性转化相关的分子相关因素 无症状的MGUS为MM或WM。这些发现将构成假设的基础，这些假设将在 CAP-MGUS中心计划从实验系统中获得更多的分子数据 在生物信息学核心中进行了分析。

Bioinformatics Core Project Summary All forms of the incurable plasma cell malignancies, multiple myeloma (MM), and Waldenstrom’s macroglobulinemia (WM) emerge from a precursor condition known as monoclonal gammopathy of undermined significance (MGUS). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion virtually indistinguishable from MM. The risk of conversion of MGUS to MM is approximately 1% per year. The mechanisms underlying the MGUS to MM or WM transformation are unclear. One possibility is that precancerous cells alter the bone marrow microenvironment and/or immune system to facilitate the conversion to overt malignancy. The Bioinformatics Core will provide in-depth genomic analysis of tissues from a spectrum of plasma cell dyscrasias, including invaluable serial samples of purified tumor cells and whole bone-marrow biopsies from patients with MGUS enrolled in observational clinical trials and followed over the past 20 years. The core will also analyze experimental samples obtained from Research Projects 1 and 2 of the Cancer Prevention-Interception Against MGUS Progression (CAP-MGUS Center) that aim to understand and treat premalignant changes in the plasma cells, immune system, and microenvironment in order to eliminate and/or delay the onset of malignant transformation. The Myeloma Center at the University of Arkansas for Medical Sciences (UAMS), where the core will be housed, is a unique resource for laboratory and clinical investigation of plasma cell dyscrasias with a long history of studying the biology of these diseases. The Bioinformatics Core will use innovative bioinformatics techniques in the context of a large clinically and molecularly annotated archive of primary plasma cell dyscrasias, to identify molecular correlates associated with the conversion of the benign asymptomatic MGUS to MM or WM. These discoveries will form the basis for hypotheses that will be tested in the CAP-MGUS Center projects, from which additional molecular data from experimental systems will be analyzed in the Bioinformatics Core.