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 mostly through PTPN11; human histiocytic sarcoma is very rare, and in the one series that looked, PTPN11 is present at lower frequency beside BRAF. Both species activate the same pathway. The dog is the premier genetic model because the disease is frequent there and rare in people.

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 · 1 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.

PTPN11 concordant

MAPK-activating driver (SHP2 phosphatase)

Dog

55.8%

of 129 tumors · somatic activating missense, predominantly E76K and G503V

Yang et al. 2024

Human

15.7%

of 19 tumors · PTPN11 hotspot mutations (3/19)

Hedan et al. 2020

The single most recurrent canine HS driver. Both species activate MAPK: PTPN11 dominates in dogs (56.75%, 63/111, Hedan 2020; 55.8%, 72/129, Yang 2024), is present at lower frequency in a small human series (15.7%, 3/19, Hedan 2020), and is tied to the visceral disseminated form in dogs. A frequency difference between species, measured on both sides; the human side is a small sample.

fused signature constraint LOEUF 0.156 ortholog dog↔human high-corroborated germline 4 ClinVar syndromes

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); rare in canine HS

Dog

0.9%

of 111 tumors · BRAF mutations orthologous to human S465T and G469A in the single mutated case (1/111); mutually exclusive with PTPN11 and KRAS in all but one composite case

Hedan et al. 2020

Human

62.5%

of 8 tumors · BRAF V600E

Go et al. 2014

Dog (cited): 0.9% (1/111, Hedan 2020), mutually exclusive with PTPN11 and KRAS; not recurrent across Takada 2019, Yang 2024, Asada 2023

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

Human HS is BRAF-driven in a small series (62.5%, 5/8, Go 2014) while canine HS carries BRAF at 0.9% (1/111, Hedan 2020) and reaches the same MAPK axis through PTPN11. Both sides measured, same gene and disease; the canine zero is now a measured rarity rather than an argument from absence, and the human number is small-n.

Human HS is BRAF-V600E-enriched in a small series (62.5%, 5/8, Go 2014). In dogs BRAF is a measured rarity (0.9%, 1/111, Hedan 2020), carrying S465T- and G469A-orthologous changes in that one case, and not recurrent across Takada 2019, Yang 2024 and Asada 2023. Both sides measured; both human series are small.

fused signature constraint LOEUF 0.237 ortholog high-corroborated

Canine-enriched drivers

darkness · 5

Recurrent in the canine cohort; the human side has no measurement on record here, either not yet searched or searched with nothing found (each card says which). Coverage darkness, not a measured disagreement (INV-81 / INV-77).

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, mutually exclusive with PTPN11 and BRAF in all but one composite case (Hedan 2020). Two cohorts, both shown: 3.1% (4/129, Yang 2024) and 7.2% (8/111, Hedan 2020). The human KRAS frequency in HS has not been searched here.

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 has not been searched here.

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 has not been searched here.

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 has not been searched here.

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 has not been searched here.