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Molecular subtypes in canine hemangiosarcoma reveal similarities with human angiosarcoma
Guannan Wang1, Ming Wu2, Amy C Durham3
1Department of Pathology and Laboratory Medicine, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Plos One
|March 27, 2020
Summary
Canine hemangiosarcoma (HSA) shares molecular similarities with human angiosarcoma (AS). Identifying driver mutations in HSA offers a valuable model for testing targeted therapies applicable to both species.
Area of Science:
- Oncology
- Comparative Pathology
- Genomics
Background:
- Angiosarcoma (AS) is a rare cancer with poor prognosis and limited treatment options.
- Canine hemangiosarcoma (HSA) is a common, aggressive cancer histologically similar to AS, making it a potential model for therapeutic development.
Purpose of the Study:
- To develop a next-generation sequencing (NGS) panel to identify driver mutations in canine hemangiosarcoma (HSA).
- To investigate molecular similarities between HSA and human angiosarcoma (AS) for potential therapeutic strategies.
Main Methods:
- Development and validation of an NGS targeted resequencing panel.
- Sequencing of 50 canine hemangiosarcoma (HSA) cases.
- Analysis of mutation patterns and downstream signaling pathways.
Main Results:
- Identified potential driver mutations in over 90% of HSA cases.
- Detected recurrent mutations in PIK3CA, PTEN, PLCG1, TP53, and NRAS, with NRAS mutations being previously undetected.
- Observed molecular similarities between HSA and AS, including shared mutations and activated oncogenic pathways (MAPK, PI3K).
Conclusions:
- Spontaneous canine hemangiosarcoma (HSA) presents distinct molecular subtypes with driver mutations mirroring those in human angiosarcoma (AS).
- HSA serves as a relevant preclinical model for evaluating targeted therapies, potentially benefiting both canine and human cancer patients.
