The COP has made significant progress on the inaugural comparative pathology effort for this new initiative in 2017. The pathology board, consisting of a joint veterinary/physician neuropathology commission of 14 members, has developed 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. A retrospective pathologic assessment of approximately 200 hematoxylin and eosin stained glass slides + a panel of 5 IHC markers treatment-naive canine gliomas of all subtypes and grades has been conducted. The CBTC membership has also proposed genomic analyses and expression profiling of a minimum 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. We have also initiated several other projects in this area, which are listed here: 1. Whole-exome sequencing of n = 50 canine meningiomas (in collaboration with Renee Chambers at UAB and Greg Tawa/NIH/NCATS 2. Survey instrument to veterinary neurologists in the US to capture the clinical landscape of canine brain tumor management 3. High-throughput drug screening of P53 w/t canine and pediatric glioma cell lines 4. A clinical trial of a novel capsize-3 activating small molecule (PAC-1) in dogs with meningioma, which is linked to assessment of a novel apoptosis-reporting PET imaging agent (in collaboration with NHLBI/IPDC, NCI/CCR/MIP, and University of Illinois. 5. MRI consensus statement on harmonization of imaging parameters for dogs enrolled in brain tumor clinical trials (manuscript in press). A follow up meeting of the CBTC membership is planned at NIH on Sept 18-19, 2017

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011696-02
Application #
9556680
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
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City
State
Country
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