Genetic Characterization of Canine Brain Tumors

National Center For Advancing Translational Sciences

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Abstract

Recent work focused on a set of 116 meningioma samples spanning 10 histological types: Grade 1 (Meningothelial, transitional, fibrous, angiomatous, psamommatous, syncytial, microcystic), Grade 2 (Chordoid, atypical), and Grade 3 (anaplastic). The samples were clustered according to similarity of gene expression. The clustering by gene expression was largely consistent with clustering according to histological subtype. However, one gene expression-based sample cluster grouped a number of histological subtypes together: Meningioma Psammomatous, Meningioma Synsytial, Meningioma Transitional, and Meningioma Meningothelial. Upon further investigation of these samples, the presence of psammoma bodies (microscopic calcifications) arose as a common theme. This and other inconsistencies required the team to review the histology for all samples. Since the goal is to find targets and therapies relevant to the various sub-types of meningioma, accurate sub-type assignments are key. In the current year, histological reassessment of all meningioma samples was completed at UC Davis. The new histological assignments proved to be more consistent with clusters based on the gene expression data previously generated by NCATS. With additional support from UCSF, DNA methylation, copy number analysis, and proteomics studies will soon be completed. These analyses, in combination with gene expression, will be used to refine the molecular level clustering. Improved agreement between refined clusters and histological assignments will validate the utility of the multi-omics approach to diagnose meningioma sub-types, define intervention targets and select drug candidates for validation in dogs and humans.