Pathology

关键基因的表观遗传沉默通过异常甲基化似乎在肿瘤中起着关键作用 发展。促进我们对癌症中基因表达的表观遗传调控的基本理解 细胞，并在临床上检验基因重新甲基化具有治疗潜力的假设，我们将 将慢性淋巴细胞白血病(CLL)作为本计划项目中提出的项目的模型进行研究 求婚。然而，有意义地进行基础研究并将重要发现转化为 大量组织样本的可获得性极大地促进了临床环境的建立 随附病理和临床资料，来源于相关患者CLL。这个核心，这个 病理/组织采购核心，通过俄亥俄州立大学白血病组织库(LTB)的合作， 将在支持本计划项目的基础和临床项目中发挥这一作用。OSU白血病 组织银行拥有完善的基础设施，直接在我们的领导下。核心将参与 为项目采购CLL细胞和CLL案例的分子特征。全 有效组织库管理的要点，包括组织收集、质量控制等活动 标本、组织储存、初始和后续样本的采购及其病理学和临床 信息、数据输入和数据库管理，以及患者同意和保密都很好 在这个核心中开发的。此外，该核心具有处理采购的样品的既定能力 纯细胞群体的制备(例如，通过CD19阳性选择的CLL细胞)、细胞裂解物、核 酸和蛋白质以统一的方式提供，以便随时分发给研究人员。此外，执行以下操作的程序 将组织优先分配给我们机构内外的大量调查人员，包括 有效地到位了。在此背景下，我们相信这一核心将在支持 本申请中提出的5个项目，以及未来的项目和协作。虽然目前提供资金 关于OSU LTB的基础设施，需要强调的是，为此申请的资金没有重叠 核心，因为此计划项目中建议的所有新工作目前都不是由NCI或其他同行资助的 审查拨款。因此，该核心的具体目标是：1)提供集中收集、处理 以及从俄亥俄州立大学治疗的CLL患者那里收集的最先进的样本储存库，包括方案 与本计划项目相关；2)提供经处理的CLL样本的材料，以支持项目 本计划项目建议书的1-5项，以及3)执行分子表征， 包括细胞遗传学荧光原位杂交(FISH)研究，lgVH和p53突变状态，所有 项目中使用的CLL病例允许随后与临床和实验室结果相关联。

Epigenetic silencing of critical genes through aberrant methylation appears to play a key role in tumor development. To advance our basic understanding of the epigenetic regulation of gene expression in cancer cells, and clinically test the hypothesis that remethylation of genes has therapeutic potential, we will investigate chronic lymphocytic leukemia (CLL) as a model in the projects presented in this program project proposal. However, the ability to meaningfully conduct basic studies and translate important findings to the clinical setting is greatly facilitated by the availability of an extensive repository of tissue samples, with accompanying pathologic and clinical data, procured from relevant patients CLL. This Core, the Pathology/Tissue Procurement Core, through the collaboration of the OSU Leukemia Tissue Bank (LTB), will serve this function in supporting the basic and clinical projects of this Program Project. The OSU leukemia tissue bank has a well-established infrastructure directly under our leadership. The Core will participate in the procurement of procurement of CLL cells and the molecular characterization of CLL cases for the Projects. All the essentials of effective tissue bank management, including the activities of tissue collection, quality control of specimens, tissue storage, procurement of initial and follow-up samples and their pathology and clinical information, data entry and database management, and patient consent and confidentiality are very well developed in this Core. In addition, this Core has the established capacity to process procured specimens for the preparation of pure cell populations (e.g., CLL cells though CD19 positive selection), cell lysates, nucleic acids and proteins in a uniform manner for ready distribution to investigators. Furthermore, the procedures for prioritizing and distributing tissue to a large base of investigators, within and outside our institution, are effectively in place. Against this background, we believe that this Core will function well in the support of the 5 projects proposed in this application, as well as future projects and collaborations. While funding currently exists for the infrastructure of OSU LTB, it is emphasized that there is no overlap in funding requested for this Core, as all of the new work proposed in this Program Project is not currently funded by NCI or other peer reviewed grants. The Specific Aims of this Core are, therefore, to: 1) provide central collection, processing and a state-of-the-art repository for samples collected from CLL patients treated at OSU, including protocols relevant to this Program Project; 2) provide materials from processed CLL samples for the support of Projects 1-5 of this Program Project proposal in a standardized manner, and 3) perform molecular characterization, including cytogenetic fluorescent in-situ hybridization (FISH) studies, lgVH and p53 mutational status, on all CLL cases used in the Projects to permit subsequent correlation with clinical and laboratory results.