Analyses of canine cancer mutations and treatment outcomes using real-world clinico-genomics data of 2119 dogs

Wu, Kevin; Rodrigues, Lucas; Post, Gerald; Harvey, Garrett; White, Mary H.; Miller, Aubrey; Lambert, Lindsay; Lewis, Benjamin M.; Lopes, Christina; Zou, James

doi:10.1038/s41698-023-00346-3

Cited by 22 publications

(28 citation statements)

References 86 publications

(118 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequencing metrics are provided in Supplementary Table 2. This sequencing data was also included in two prior pan‐cancer publications or preprints as a subset of a much larger set of tumour sequencing information for a diverse set of canine cancers 30,31 …”

Section: Methodsmentioning

confidence: 99%

“…This sequencing data was also included in two prior pan-cancer publications or preprints as a subset of a much larger set of tumour sequencing information for a diverse set of canine cancers. 30,31 Single-nucleotide variants (SNVs) and insertions and deletions (indels) were identified by creating a pileup file in SAMtools 32 and calling variants using Varscan2, 33 filtering out variants with coverage <10Â, variant allele fraction (VAF) < 1% and quality score <20. Additional filtering was performed to flag variants with VAF < 2% or >95% (potential sequencing artefacts or homozygous germline variants) and to remove variants located in repetitive regions.…”

Section: Tumour Sequencingmentioning

confidence: 99%

See 1 more Smart Citation

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Estabrooks,

Gurinovich,

Pietruska

et al. 2023

Vet Comparative Oncology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Tumour Sequencingmentioning

confidence: 99%

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Estabrooks,

Gurinovich,

Pietruska

et al. 2023

Vet Comparative Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Such comprehensive mutation landscape data has become increasingly available as more tumors have been profiled using genome‐wide approaches 12‐17 . Furthermore, a recent real‐world clinical genomics study provides an early compelling view of the untapped potential in genomics and precision medicine for dogs with cancer 18 . This study uncovered gene‐level prognostic indications for several cancer genes and the potential association of mutant genes with response to targeted treatments, based on point mutation detection in 48 genes.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14][15][16][17] Furthermore, a recent realworld clinical genomics study provides an early compelling view of the untapped potential in genomics and precision medicine for dogs with cancer. 18 This study uncovered gene-level prognostic indications for several cancer genes and the potential association of mutant genes with response to targeted treatments, based on point mutation detection in 48 genes. However, more data is needed to expand the breadth and depth of genomic data utilization for the management of cancer in dogs, including assessment of a broad spectrum of cancer genes and key mutation types, mutation-level clinical relevance, and, particularly, for assessment of treatment responses in dogs with cancer that are treated based on genomic biomarker information.…”

Section: Introductionmentioning

confidence: 99%

Novel genomic prognostic biomarkers for dogs with cancer

Chon,

Sakthikumar,

Tang

et al. 2023

Veterinary Internal Medicne

View full text Add to dashboard Cite

BackgroundGrowing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery.HypothesisAnalyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value.AnimalsA total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available.MethodsClinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression‐free survival (PFS). The log‐rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression.ResultsCombined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05).Conclusion and Clinical ImportanceWe identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer.

show abstract

“…[8][9][10] Mounting evidence supports the substantial utility of genomics in the clinical management of canine cancer patients. [11][12][13] Over the past decade, genomic characterization of canine cancers and the exploration of mutation-based biomarker discovery efforts have expanded significantly. Close to 150 peer-reviewed publications now describe genomic investigations of canine cancers, encompassing thousands of canine cancer genomes.…”

mentioning

confidence: 99%

Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential

Sakthikumar,

Warrier,

Whitley

et al. 2023

Vet Comparative Oncology

View full text Add to dashboard Cite

A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation‐based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics‐guided medicine in canine oncology, we have developed and validated a canine cancer next‐generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation‐based biomarkers in veterinary oncology.

show abstract

Analyses of canine cancer mutations and treatment outcomes using real-world clinico-genomics data of 2119 dogs

Cited by 22 publications

References 86 publications

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

Novel genomic prognostic biomarkers for dogs with cancer

Genomic analysis across 53 canine cancer types reveals novel mutations and high clinical actionability potential

Contact Info

Product

Resources

About