Comparative oncology / research surface

Glioma: the dog as a natural model of human disease.

Canine glioma is a natural model of human glioma, and Amin et al. 2020 showed it resembles human PEDIATRIC glioma most closely, by mutation rate, aneuploidy, and DNA-methylation class (78% classify as pediatric). Both share recurrent drivers across the receptor-tyrosine-kinase, PI3K, and cell-cycle pathways. Below is the canine somatically-altered driver landscape, cited to that cohort. These are somatic tumor alterations reported as cohort frequencies, a portrait of the disease across dogs, never a germline carrier status and never an individual-dog prediction.

These are somatic tumor alterations, not a germline carrier status. Every number here is a cohort frequency, the fraction of sequenced tumors somatically altered in a gene, reported by a published study. It is not a variant a dog inherits or carries, and it is not a prediction about any individual dog. Cross-species labels (concordant, divergent, canine-enriched) come from a commensurability-gated concordance map (INV-81), not a coarse shared flag.

This is the molecular driver landscape for this cancer. all cancers →

The conserved core

concordant · 5 genes

Drivers where dog and human agree on status for this comparable cancer (commensurability-gated). That agreement is the evidence the dog models the human disease here.

PDGFRA concordant

receptor tyrosine kinase; the dominant canine glioma driver and an established human glioma driver, focally co-amplified with KIT and MYC across the shared syntenic block

Dog

16%

of 67 tumors · focal co-amplification (PDGFRA/KIT/MYC block)

Amin et al. 2020

Human

—

rate not tabled (see basis)

Human basis: core recurrent RTK driver of human glioma (Amin 2020); exact human rate not separately tabled.

Also a recurrent K385I/M hotspot mutation in 6/81 (7.4%). A core shared driver of human glioma; canine and human converge on RTK activation.

fused signature constraint LOEUF 0.264 ortholog dog↔human high

PIK3CA concordant

oncogene; PI3K catalytic subunit; the H1047R/L hotspot shared with human glioma and many human cancers

Dog

9.9%

of 81 tumors · H1047R/L hotspot mutation

Amin et al. 2020

Human

—

rate not tabled (see basis)

Human basis: PI3K-pathway activation shared with human glioma (Amin 2020).

PI3K-pathway activation is shared between canine and human glioma.

fused signature constraint LOEUF 0.221 ortholog dog↔human high-corroborated germline 5 ClinVar syndromes

CDKN2A/B concordant

cell-cycle tumor suppressor (INK4/ARF); homozygous deletion, a recurrent driver in both canine and human glioma

Dog

12%

of 67 tumors · homozygous deletion

Amin et al. 2020

Human

—

rate not tabled (see basis)

Human basis: cell-cycle disruption via CDKN2A/B loss shared with human glioma (Amin 2020).

Cell-cycle disruption via CDKN2A/B loss is shared with human glioma.

fused signature constraint LOEUF 1.836 ortholog dog↔human high-corroborated

IDH1 concordant

the R132 hotspot is the hallmark of ADULT human glioma; its LOW frequency in canine glioma is the honest tell that canine glioma resembles PEDIATRIC human glioma, where IDH1 is also rare

Dog

3.7%

of 81 tumors · R132C hotspot mutation

Amin et al. 2020

Human

—

rate not tabled (see basis)

Human basis: IDH1 R132 defines adult low-grade human glioma; rare in pediatric (Amin 2020).

IDH1 R132 defines adult low-grade human glioma (majority) but is rare in pediatric glioma. Canine glioma's 3.7% places it with pediatric, consistent with the methylation classification.

fused signature constraint LOEUF 0.829 ortholog dog↔human high-corroborated

PTEN concordant

PI3K/mTOR tumor suppressor; a recurrent driver in both canine and human glioma

Dog

of 67 tumors · homozygous deletion (arm-level loss additionally in 14%)

Amin et al. 2020

Human

—

rate not tabled (see basis)

Human basis: PTEN loss reinforces the PI3K axis shared with human glioma (Amin 2020).

PTEN loss reinforces the PI3K axis shared with human glioma.

fused signature constraint LOEUF 0.685 ortholog dog↔human high germline 14 ClinVar syndromes