Comparative oncology / research surface

Histiocytic sarcoma: the dog as the model of a human-rare cancer.

Canine histiocytic sarcoma is concentrated in specific breeds and reaches MAPK activation through PTPN11 rather than the BRAF that defines the human disease. Human histiocytic sarcoma is very rare, which is exactly why the dog is its premier genetic model. The comparison is convergent pathway, divergent gene.

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 →

Where dog and human diverge

divergent · 1

Both sides characterized for a commensurable lesion, and they disagree. The honest limit of the model, not darkness and not a missing rate filled with zero.

BRAF divergent

human MAPK driver (V600E); the canine anchor of divergence

Dog

—

see cited basis

Human

62.5%

of 8 tumors · BRAF V600E

Go et al. 2014

Dog (cited): not recurrently mutated across canine HS sequencing cohorts (Takada 2019, Yang 2024, Asada 2023)

Human (cited): 62.5% BRAF V600E (5/8, Go 2014)

The headline divergence of the vertical: human HS is BRAF-driven while canine HS reaches the same MAPK axis via PTPN11. Both sides characterized (canine as sequenced-and-absent, human as 62.5%), same gene + disease. Caveat: canine negativity is argument-from-absence and the human number is small-n.

The headline cross-species divergence: human HS is BRAF-V600E-enriched (5/8, Go 2014) while canine HS reaches the same MAPK axis through PTPN11 instead. Canine BRAF-negativity is argument-from-absence across three sequencing cohorts, and the human number is small-n.

fused signature constraint LOEUF 0.237 ortholog high-corroborated

Canine-enriched drivers

darkness · 6

Recurrent in the canine cohort; the human side is not established as a recurrent driver here or is unquantified. Coverage darkness, not a measured disagreement (INV-81 / INV-77).

PTPN11 canine-enriched

55.8% of 129

MAPK-activating driver (SHP2 phosphatase) · somatic activating missense, predominantly E76K and G503V · Yang et al. 2024

The single most recurrent canine HS driver, and the clearest gene-level cross-species divergence: canine HS activates MAPK through PTPN11/SHP2, whereas human HS has no quantified PTPN11 signal and instead uses BRAF.

KRAS canine-enriched

3.1% of 129

RAS/MAPK driver · somatic activating missense, predominantly Q61H · Yang et al. 2024

A minor second MAPK node in canine HS that reinforces the same pathway the human disease reaches through BRAF.

CDKN2A/B canine-enriched

62.8% of 86

tumor-suppressor loss (MTAP-CDKN2A/B locus) · recurrent genomic deletion at CFA 11q16 · Hedan et al. 2011

The most frequent canine HS copy-number event; the same locus carries the germline susceptibility signal in predisposed breeds. The human somatic HS frequency is unquantified.

RB1 canine-enriched

55.8% of 86

cell-cycle tumor-suppressor loss · recurrent copy-number loss at the RB1 locus (CFA 22) · Hedan et al. 2011

Highly recurrent, with a strong genetic-background effect: 83.3% loss in Flat-Coated Retrievers versus 41.1% in Bernese. The human side is unquantified.

PTEN canine-enriched

40.7% of 86

PI3K-AKT tumor-suppressor loss · recurrent copy-number loss at the PTEN region (CFA 26) · Hedan et al. 2011

Consistent with the AKT-pathway activation reported alongside ERK in canine HS (Asada 2023). The human side is unquantified.

TP53 canine-enriched

40% of 5

tumor suppressor · somatic frameshift / loss-of-function · Asada et al. 2023

Low-confidence: the 40% somatic-mutation figure rests on an n=5 exome cohort (Asada 2023). The copy-number evidence (Hedan 2011) is more robust. The human side is unquantified.