The ingaural meeting helped to focus the group on projects that were felt to have the largest immediate impact and ability to galvanize the field. To that end, the COP has planned and secured CCR support for a comparative pathology initiative to begin in Q1Y2016 to establish the translational relevance of canine glioma as a model for human glioma. This initiative also includes collaboration with Mark Simpson, Director of the Comparative Molecular Pathology unit of NCI/CCR/ Laboratory of Cell Biology and Genetics. Collection of tissues and sharing of data for public dissemination to advance these goals is optimally facilitated by the COP. The project will begin with the development of an updated grading and classification scheme for canine gliomas to promote uniformity in diagnosis across institutions and improve making comparisons with human adult and pediatric glial tumors. This initiative is envisioned to take place in 2 distinct phases: first, a retrospective pathologic assessment of approximately 200 hematoxylin and eosin stained glass slides of treatment-naive canine gliomas of all subtypes and grades by both veterinary and physician neuropathologists from multiple participating institutions. High resolution images will be centrally scanned and hosted digitally, and a consensus panel of a minimum of 6 of each physician and veterinary pathologists would develop a consensus on clear, concise criteria for classification and grading; these should be based whenever possible on the current human WHO system to allow for comparison, but should incorporate species-specific features as identified and agreed upon. A subgroup of tumors (formalin-fixed paraffin-embedded tissue) that were optimally stored and characterized for this review would then be selected for expression of pertinent molecular markers (such as GFAP, vimentin, Olig2, CNPase, synaptophysin, Neurofilament M, NeuN/beta-III tubulin/NF, and Ki67). This will be performed using immunohistochemistry to allow further uniformity in diagnosis and comparison with human adult and pediatric glial tumors. This component of the work is estimated to begin in Q2Y2016. The CBTC membership has also proposed genomic analyses and expression profiling of 50 canine high-grade gliomas meeting these newly revised classification criteria to allow for comparison with human adult and pediatric glial tumors, and to generate potential pharmacologic targets for canine patients. This project will be both retrospective and prospective in nature. For the retrospective portion, snap-frozen tissue from institutions with paired banked FFPE tissue from histopathology-confirmed glial tumors that have been confirmed within the newly proposed grading and classification scheme, will be subjected to whole-exome sequencing and RNA-seq. For the prospective portion, kits and detailed SOPs will be distributed to selected sites, both academic institutions and private practices, for the collection of tumor specimens. Samples will be snap-frozen tissue or tissue in RNA-later and formalin-fixed tissue, stored at a central biobank location, and subjected to histopathological confirmation, whole-exome sequencing and RNA-sequencing as funding is available. Sequence information will be subjected to informatics, processed, and shared publicly as soon as publication-ready. The COP's role will be to coordinate collection of tissues and partner with an academic leader within the CBTC network to determine the optimal location for the sequencing and informatics work, and will provide programmatic support to the project.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011696-01
Application #
9344042
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Budget End
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
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