Pathology

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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.