Title

Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.

Document Type

Article

Publication Date

2-10-2020

Keywords

JGM, JMG

JAX Source

Cancer Cell 2020 Feb 10;37(2):243-257.e7

PMID

32049048

DOI

https://doi.org/10.1016/j.ccell.2020.01.004

Grant

CA16672,CA034196,CA190121,CA226387, JAX Scholar Program, American Cancer Society Fellowship

Abstract

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132. Canine gliomas showed high similarity with human pediatric gliomas per robust aneuploidy, mutational rates, relative timing of mutations, and DNA-methylation patterns. Our cross-species comparative genomic analysis provides unique insights into glioma etiology and the chronology of glioma-causing somatic alterations.

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