Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma.

Area of Science:

• Comparative oncology
• Genomics
• Cancer biology

Background:

• Angiosarcoma is an aggressive cancer with poor outcomes, hindered by rarity and heterogeneity.
• Canine hemangiosarcoma shares clinical similarities with human angiosarcoma, especially in high-risk breeds like golden retrievers.

Purpose of the Study:

• To investigate the genomic landscape of canine hemangiosarcoma.
• To determine if canine hemangiosarcoma serves as a relevant model for human angiosarcoma.
• To identify shared genomic alterations and mutational signatures between canine and human angiosarcomas.

Main Methods:

• Whole-exome sequencing of 47 golden retriever hemangiosarcomas.
• RNA sequencing of 74 hemangiosarcomas from multiple breeds.
• Comparison of canine genomic data with human angiosarcoma data from The Angiosarcoma Project.

Main Results:

• Somatic mutations frequently occurred in TP53 (59.6%), PIK3CA (29.8%), and PIK3R1 (8.5%).
• The predominant mutational signature was age-associated cytosine to thymine deamination.
• Recurrent deletions of CDKN2A/B and gains of VEGFA, KDR, and KIT were observed, mirroring human angiosarcoma findings.

Conclusions:

• Canine hemangiosarcoma exhibits a genomic landscape highly similar to human breast and visceral angiosarcomas.
• Dogs represent a valuable preclinical model for advancing angiosarcoma research and therapeutic development.
• Shared genomic etiology underscores the potential of comparative oncology in understanding rare and aggressive human cancers.