Chromosomal aberrations in canine gliomas define candidate genes and common pathways in dogs and humans

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of highgrade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy.

Original languageEnglish (US)
Pages (from-to)700-710
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number7
DOIs
StatePublished - Jul 1 2016

Keywords

  • Astrocytoma
  • Brain tumor
  • Cancer genomics
  • Copy number alteration
  • Dog
  • Glioma
  • Oligodendroglioma
  • Single nucleotide polymorphism (SNP)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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