Pathology

通过异常甲基化导致的关键基因的表观遗传沉默似乎在肿瘤中起着关键作用 发展促进我们对癌症基因表达的表观遗传调控的基本理解 细胞，并在临床上测试基因再甲基化具有治疗潜力的假设，我们将 研究慢性淋巴细胞白血病（CLL）作为本项目中提出的项目的模型 提议然而，有意义地进行基础研究并将重要发现转化为 由于可获得广泛的组织样本储存库， 附病理和临床数据，从相关患者CLL获得。这个核心， 病理学/组织采购核心，通过OSU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 组织库有一个完善的基础设施，直接在我们的领导下。核心将参加 为项目采购CLL细胞和CLL病例的分子表征。所有 有效组织库管理的要素，包括组织采集、质量控制 标本、组织储存、初始和随访样本的获取及其病理学和临床 信息、数据输入和数据库管理以及患者同意和保密性都非常好 在这个核心中发展。此外，该中心还具备处理采购标本的既定能力， 纯细胞群的制备（例如，CLL细胞通过CD 19阳性选择），细胞裂解物，核酸 酸和蛋白质以统一的方式准备分发给研究人员。此外， 优先考虑和分发组织给我们机构内外的大量研究人员， 有效到位。在这一背景下，我们认为，这一核心将在支持联合国 本申请中提出的5个项目，以及未来的项目和合作。虽然目前资金 OSU LTB的基础设施存在，需要强调的是， 核心，因为本计划项目中提出的所有新工作目前都没有得到NCI或其他同行的资助 审查赠款。因此，本核心的具体目标是：1）提供中央收集、处理 和一个最先进的储存库，用于收集在俄勒冈州立大学治疗的CLL患者的样本，包括方案 与本计划项目相关; 2）提供来自已处理CLL样品的材料，以支持项目 1-5以标准化的方式，和3）进行分子表征， 包括细胞遗传学荧光原位杂交（FISH）研究、lgVH和p53突变状态， 项目中使用的慢性淋巴细胞白血病病例，以便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.