Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Abstract

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.

The K9 lymphoma assay allows a genetic subgrouping of canine lymphomas with improved risk classification

“…The K9 lymphoma assay, covering a total of 196 kbp, was designed and built to interrogate 31 genes recurrently mutated in canine lymphomas [8][9][10] , as well as oncogenes and tumor suppressor genes mutated in other canine tumors [14][15][16][17][18][19][20][21] (Table 1). An in silico validation of the panel utilizing the data of 77 dogs with DLBCL previously analyzed by WES 10 demonstrated that the panel identified at least one mutation in 89.6% of cases (Supplementary Data 4).…”

Review of Molecular Technologies for Investigating Canine Cancer

“…Indeed, several recent studies in the canine oncology field have demonstrated the strong clinical impact that oncogenomics can have. For example, genomic analysis of 191 dogs with splenic haemangiosarcoma identified both the somatic mutations and germline variants associated with clinical variables, including breed and overall survival [ 1 ], while genomic analysis of 828 dogs across 53 tumour types found that almost 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications [ 2 ]. In another study of 127 dogs for which genomic analysis and clinical outcomes were available, mutations in 6 genes were significantly associated with shorter progression-free survival (PFS; CND1 , CCND3 , SMARCB1 , FANCG , CDKN2A/B , and MSH6 ), and dogs that received targeted treatment before first progression showed significantly longer PFS than those that did not, including those dogs that received genomically informed targeted treatment [ 3 ].…”