Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma.
angiosarcoma
doxorubicin
genomics
hemangiosarcoma
precision medicine
targeted sequencing
Journal
Veterinary and comparative oncology
ISSN: 1476-5829
Titre abrégé: Vet Comp Oncol
Pays: England
ID NLM: 101185242
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
11
07
2023
received:
23
11
2022
accepted:
12
07
2023
pubmed:
22
9
2023
medline:
22
9
2023
entrez:
21
9
2023
Statut:
ppublish
Résumé
Canine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells with short survival times. Understanding the genomic landscape of HSA may aid in developing therapeutic strategies for dogs and may also inform therapies for the rare and aggressive human cancer angiosarcoma. The objectives of this study were to build a framework for leveraging real-world genomic and clinical data that could provide the foundation for precision medicine in veterinary oncology, and to determine the relationships between genomic and clinical features in canine splenic HSA. One hundred and nine dogs with primary splenic HSA treated by splenectomy that had tumour sequencing via the FidoCure® Precision Medicine Platform targeted sequencing panel were enrolled. Patient signalment, weight, metastasis at diagnosis and overall survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables including outcome were assessed. Somatic mutations in TP53 (n = 44), NRAS (n = 20) and PIK3CA (n = 19) were most common. Survival was associated with presence of metastases at diagnosis and germline variants in SETD2 and NOTCH1. Age at diagnosis was associated with somatic NRAS mutations and breed. TP53 and PIK3CA somatic mutations were found in larger dogs, while germline SETD2 variants were found in smaller dogs. We identified both somatic mutations and germline variants associated with clinical variables including age, breed and overall survival. These genetic changes may be useful prognostic factors and provide insight into the genomic landscape of hemangiosarcoma.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
623-633Subventions
Organisme : PETCO Foundation
Informations de copyright
© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.
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