What question did this study set out to answer?

The study aims to explore the genomic similarities between human angiosarcoma and canine hemangiosarcoma to enhance therapeutic strategies.

April 5, 2026

Abstract 5572: Conservation of driver mutations and oncogenic pathway alterations revealed through a comparative genomic analysis of human angiosarcoma and canine hemangiosarcoma

Key Points

The study aims to explore the genomic similarities between human angiosarcoma and canine hemangiosarcoma to enhance therapeutic strategies.
Integrative genomic analyses of human angiosarcoma cohorts using cBioPortal
Large-scale genomic profiling of canine hemangiosarcoma samples from FidoCure
Cross-species comparison of mutation hotspots and pathway alterations
Common mutations identified in TP53, PIK3CA, and others in both species
Mutations clustered in specific domains suggest pathways being activated
Convergent loss of tumor-suppressor function noted in TP53 alterations
Similar disruptions of key signaling pathways across species observed

Abstract

Abstract Angiosarcoma (AS) is a rare and aggressive endothelial malignancy, representing 2% of soft tissue sarcomas in humans. Progress in developing effective therapies has been hindered by its low incidence, genomic heterogeneity, and the scarcity of representative preclinical models.Integrative genomic analyses of two cBioPortal cohorts (n=131) identified recurrent alterations in TP53 (26%), KDR (17.6%), POT1 (17.6%), PIK3CA (14.5%), FLT4 (11.5%), PTPRB (11.5%), and NRAS (5.3%), highlighting pervasive disruptions of DNA damage response, PI3K/AKT/mTOR, and angiogenic receptor signaling. However, the rarity of AS limits functional validation and biomarker-driven therapy development.Canine hemangiosarcoma (HSA) is a biologically analogous vascular tumor that occurs spontaneously with far higher incidence, offering a unique opportunity to model AS in an immunocompetent host. Large-scale profiling of HSA from the FidoCure Precision Medicine Platform (n=1,177) revealed overlapping mutations in TP53 (54.9%), PIK3CA (29.9%), NRAS (15.3%), FLT4 (3.6%), PTEN (3.4%), and KDR (2.6%), mirroring the human landscape.Cross-species analyses showed striking molecular parallels. PIK3CA mutations in both species clustered in the helical and kinase domains, consistent with pathway activation. While mutation at the canonical hotspot (H1047R/L/Y) predominated in HSA, AS was found to harbor heterogeneous variants (P124L, T957P, M1043V/I). TP53 variants localized to conserved DNA-binding regions (human R175, R248, R273; canine R164H, C228R/Y, R263H, R272H), indicating convergent loss of tumor-suppressor function. KDR, NRAS, and PTEN alterations similarly disrupted VEGFR2, RAS/MAPK, and PI3K signaling pathways across species.Collectively, these findings reveal deep evolutionary conservation of molecular drivers in vascular sarcomagenesis. Canine HSA faithfully recapitulates the genetic complexity and therapeutic vulnerabilities of human AS, establishing a robust comparative platform for biomarker discovery, targeted therapy validation, and translational oncology research within an immunocompetent context. Citation Format: Lucas Rodrigues, Garrett Harvey, Gerald Post, Benjamin Lewis, Abigail Hull, Aubrey O'Grady, Lindsay Lambert, Christina Lopes, Thaddeus Allen. Conservation of driver mutations and oncogenic pathway alterations revealed through a comparative genomic analysis of human angiosarcoma and canine hemangiosarcoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5572.

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