Comparative Molecular Life History of Spontaneous Canine and Human Gliomas

Abstract

Highlights d Genomic, epigenomic, and transcriptomic characterization of sporadic glioma in dogs d Somatic alterations in canine glioma converge with human glioma drivers d Canine glioma resemble pediatric human glioma by mutation rate and DNA methylation d Microenvironment similarity between canine and human pediatric and adult glioma

Canine tumor mutation rate is positively correlated with TP53 mutation across cancer types and breeds

“…We performed a rigorous quality control (QC) on the WES data published for 601 canine cases. The 601 canine cases consist of over six cancer types, including mammary cancer 13 , oral melanoma 11 , osteosarcoma 15 , lymphoma 16 , glioma 12 and hemangiosarcoma 17 (Table S1). They represent over 35 breeds (Table S1A).…”

“…They represent over 35 breeds (Table S1A). Their WES data were generated by different groups, using different exome-capturing kits and Illumina sequencing machines [11][12][13][15][16][17] . We hence performed a rigorous QC to ensure that each study met a set of quality standards before any further integrative analysis.…”

“…Among these cancers, the mammary cancer study 13 has the most comprehensive case information provided in the SRA database and related publications [11][12][13][15][16][17] (Table S1). It has not only the patient info (e.g., age, sex, breed), but also histological subtypes and limited clinic data (e.g., tumor invasiveness, patient alive/death status).…”

“…Do the same hold true for canine cancers? A recent study reports similar mutation rates for mucosal melanoma between the two species 11 , while another study reports that canine and pediatric glioma are closer in mutation rate than canine and adult glioma 12 .…”

“…To answer these questions, we performed a pan-cancer and pan-breed study with 710 canine cases with public whole exome sequencing (WES) and/or whole genome sequencing (WGS) data [11][12][13][14][15][16][17][18][19][20][21][22] . We used 601 cases with WES data [11][12][13][15][16][17] for discovery, and 18 with WES data 18,23 and 91 with WGS data [18][19][20][21][22] for validation. We also compared our canine findings to those published for the corresponding human cancers 3,4,[24][25][26][27] .…”