Specimen Acquistition and Expression Profiling

髓系白血病患者临床标本的可控性采集和处理 骨髓增生异常综合征仍然是一项关键活动，以准确、有效和全面 获取该计划项目所需的基因组数据。同样，一个受质量控制和 与此相对应的标准化肿瘤基因表达、基因拷贝数和基因分型数据 标本将继续有助于阐明急性心肌梗死的基因组基础。程序上的改进和 在受监管的实验室环境中运行微阵列分析平台将进一步为此做好准备 用于白血病患者的基于分子的临床试验的技术。因此，这 CORE有两个具体目标： 具体目标1：我们将收集、存储和处理所有患有AFP的患者的组织标本 在这个机构看到的AML和MDS的诊断。我们将包括来自骨骼的恶性细胞群 骨髓抽吸物和外周血以及皮肤穿孔活检和口腔灌洗标本 代表非恶性细胞群体。血清和血浆将被收集用于未来的蛋白质组学 生物标志物研究。将在每个患者的整个病程中收集样本(初始 提交、缓解、复发)，并在适当的情况下，以前恶性肿瘤的档案标本将 被取回。标本将被加工成细胞RNA，基因组DNA，全基因组扩增DNA， 以及每项研究所需的蛋白质提取物。细胞种群也将在未来被明显冻结 异种移植研究。特别注意样本采购(例如，白血病细胞的快速处理以 保存成绩单档案)和质量控制。 具体目标2：使用Affymetrix基因芯片平台，我们将生成完整的基因组 在本研究期间收集的所有AML样本的表达、拷贝数和等位基因丢失数据， 根据国家认可的实验室指南。Affymetrix全基因组(U133Plus2)和外显子特异性 表达阵列将用于生成定量和定性转录图谱，而 将使用全基因组基因分型(500K和1M SNP)阵列同时生成生殖系 来自肿瘤和非恶性肿瘤的基因数据、体细胞拷贝数变化数据和等位基因丢失(LOH)数据 样本对。重点将放在开发快速扭亏为盈的新方法上。

The controlled collection and processing of clinical specimens from patients with myeloid leukemia and myelodysplastic syndrome continues to be a critical activity for the accurate, efficient, and comprehensive acquisition of genomic data required for this program project. Similarly, a repository of quality controlled and standardized tumor gene expression, gene copy number, and genotyping data corresponding to these specimens will continue to aid in elucidating the genomic basis of AMI. Procedural enhancements and operation of microarray analytical platforms in a regulated laboratory environment will further prepare this technology for use in the context of molecular-based clinical trials for leukemia patients. Accordingly, this Core has two Specific Aims: Specific Aim 1: We will collect, store, and process tissue specimens from all patients with a diagnosis of AML and MDS seen at this institution. We will include malignant cell populations from bone marrow aspirates and peripheral blood as well as skin punch biopsy and buccal lavage specimens representing non-malignant cell populations. Serum and plasma will be collected for future proteomic biomarker studies. Specimens will be collected throughout each patient's disease course (initial presentation, remission, relapse) and where appropriate, archival specimens from previous malignancies will be retrieved. Specimens will be processed to cellular RNA, genomic DMA, whole genome amplified DNA, and protein extracts as required for each study. Cellular populations will also be viably frozen for future xenograft studies. Particular attention to specimen procurement (e.g. rapid processing of leukemia cells to preserve transcript profiles) and quality control will be practiced. Specific Aim 2: Using the Affymetrix GeneChip¿ platform, we will generate whole genome expression, copy number, and allelic loss data from all AML specimens collected during this study, under nationally accredited laboratory guidelines. Affymetrix whole genome (U133Plus2) and exonspecific expression arrays will be used to generate quantitative and qualitative transcriptional profiles while whole genome genotyping (500K and 1M SNP) arrays will be used to simultaneously generate germline genotype data, somatic copy number change data, and allelic loss (LOH) data from tumor and non-malignant sample pairs. Emphasis will be place on developing new methods for rapid turnaround.