American Association for Cancer Research
Browse
15417786mcr190221-sup-217824_2_supp_5870942_q10zxj.xlsx (80.54 kB)

Supplemental Table 7 from Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma

Download (80.54 kB)
dataset
posted on 2023-04-03, 17:21 authored by Kate Megquier, Jason Turner-Maier, Ross Swofford, Jong-Hyuk Kim, Aaron L. Sarver, Chao Wang, Sharadha Sakthikumar, Jeremy Johnson, Michele Koltookian, Mitzi Lewellen, Milcah C. Scott, Ashley J. Schulte, Luke Borst, Noriko Tonomura, Jessica Alfoldi, Corrie Painter, Rachael Thomas, Elinor K. Karlsson, Matthew Breen, Jaime F. Modiano, Ingegerd Elvers, Kerstin Lindblad-Toh

Supplemental Table 7

Funding

American Kennel Club Canine Health Foundation

NIH

Masonic Cancer Center, University of Minnesota

Cancerfonden

NCCF

Morris Animal Foundation

NCI

History

ARTICLE ABSTRACT

Angiosarcoma is a highly aggressive cancer of blood vessel–forming cells with few effective treatment options and high patient mortality. It is both rare and heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from a similar cancer, called hemangiosarcoma, with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. If the clinical similarity of canine hemangiosarcoma and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine hemangiosarcoma via whole-exome sequencing (47 golden retriever hemangiosarcomas) and RNA sequencing (74 hemangiosarcomas from multiple breeds). Somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). The predominant mutational signature was the age-associated deamination of cytosine to thymine. As reported in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. We compared the canine data to human data recently released by The Angiosarcoma Project, and found many of the same genes and pathways significantly enriched for somatic mutations, particularly in breast and visceral angiosarcomas. Canine hemangiosarcoma closely models the genomic landscape of human angiosarcoma of the breast and viscera, and is a powerful tool for investigating the pathogenesis of this devastating disease. We characterize the genomic landscape of canine hemangiosarcoma and demonstrate its similarity to human angiosarcoma.

Usage metrics

    Molecular Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC