Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans
Peter J Dickinson1, Dan York2, Robert J Higgins2
1From the Departments of Surgical and Radiological Sciences (PJD, DY, RAL), Pathology, Microbiology and Immunology (RJH), and Population Health & Reproduction (DB), School of Veterinary Medicine, University of California, Davis, and Bioinformatics Core, UC Davis Genome Center (NJ) University of California, Davis, California. pjdickinson@ucdavis.edu.
Journal of Neuropathology and Experimental Neurology
|June 3, 2016
Summary
Canine gliomas share genetic similarities with human brain tumors, offering a valuable model for comparative studies. Recurrent chromosomal alterations in dogs highlight key genes and pathways relevant to gliomagenesis and potential therapies.
Area of Science:
- Comparative oncology
- Genomics
- Canine cancer research
Background:
- Spontaneous canine gliomas closely resemble human gliomas in incidence and biology.
- Dogs offer a translational model for understanding brain tumor development and testing therapies.
Purpose of the Study:
- To define copy number alterations in canine gliomas.
- To identify recurrent chromosomal aberrations and their association with specific glioma subtypes.
- To compare canine glioma genetic events with human orthologues for insights into gliomagenesis.
Main Methods:
- Utilized Illumina 170K single nucleotide polymorphism arrays to analyze copy number alterations in 38 canine gliomas.
- Classified gliomas into types including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas.
- Investigated chromosomal events, gene loci (INK4A/B, RB1), and gene amplifications (PDGFRA).
Main Results:
- Identified highly recurrent chromosomal alterations in up to 85% of certain canine glioma types, notably on chromosomes 13, 22, and 38.
- Gliomas clustered into two main groups: high-grade astrocytomas (IV) and oligodendrogliomas/other tumors.
- Specific aberrations included INK4A/B loss in glioblastoma and RB1 loss/PDGFRA amplification in oligodendrogliomas.
- Canine glioma aberrations frequently involved genes in TP53, RB1, and RTK/RAS/PI3K pathways, critical in human gliomas.
- Oligodendrogliomas showed chromosomal losses syntenic to human 1p, affecting tumor suppressor genes (e.g., CDKN2C) and genes involved in apoptosis and chemoresistance.
Conclusions:
- Canine gliomas exhibit recurrent chromosomal aberrations that mirror human counterparts, validating their use as a translational model.
- Comparative analysis of chromosomal aberrations provides insights into conserved and novel pathways in gliomagenesis.
- Understanding these genetic similarities can inform therapeutic strategies for both canine and human brain tumors.
Keywords:
AstrocytomaBrain tumorCancer genomicsCopy number alterationDogGliomaOligodendrogliomaSingle nucleotide polymorphism (SNP).
