Biology subjects

Megquier, K.

Publications and source records attributed to Megquier, K..

5 recordsLinked to original sources

bioRxiv2026

Blood biomarkers and breed genetics of aging in pet dogs

Pet dogs share human-like environments while aging on a compressed timescale, making them a powerful translational model for aging research. Using genomic and phenotypic data from 7,627 dogs in the Dog Aging Project, including 976 profiled for 159 blood metabolites and clinical analytes, we generated the first GWAS catalog in dogs. Blood traits map to orthologous loci in dogs and humans, indicating deeply conserved pathways. Breed ancestry explains substantial variance in blood traits, and selection on visible characteristics such as fur type has pleiotropic metabolic effects. Leveraging mosaic ancestry in mixed-breed dogs and longitudinal mortality data, we identify blood traits elevated in short-lived breeds that predict individual mortality risk -- including globulin and potassium -- and protective traits enriched in long-lived breeds, such as ethanolamine. Although some aging-associated traits relate to growth hormone pathways, many do not, indicating that aging in dogs is multifactorial. These findings establish dogs as a translational system for identifying genetic determinants and biomarkers of aging relevant to extending healthy lifespans.

genetics↗

bioRxiv2026

Multi-omic Longitudinal Analysis of Canine Osteosarcoma Identifies Inter-Patient Heterogeneity and Immune Enrichment in Metastatic Lesions

Osteosarcoma (OS) exhibits substantial genomic complexity and inter-patient heterogeneity, necessitating longitudinal, patient-matched analyses to understand acquired features of tumor evolution. However, most published OS data is limited to primary tumor samples, limiting insight into patient-specific resistance mechanisms. To address this, we characterized the genomic landscape of paired primary and metastatic tumor samples from dogs with spontaneous OS. Whole-genome and single-cell RNA sequencing reveal mutation and gene expression profiles that are predominantly organized by patient identity. Mutational burden and pathway alterations such as those involving PI3K, NOTCH, TP53, MAPK, RAS and epigenetic regulation differ between primary and metastatic samples. Variants present in tumor tissue are readily detectable in paired cfDNA samples, demonstrating the utility of this assay for identifying tumor-specific alterations associated with treatment resistance. Analysis of bulk RNA-seq data to estimate cell-type composition shows greater immune cell representation in metastases, underscoring the importance of immune signaling pathways in OS. These findings exemplify the presence of patient-specific alterations in genomic architecture over the course of tumor progression, linking CNV amplification, pathway reprogramming, and immune evasion in metastatic OS.

genomics↗

bioRxiv2024

Impact of preanalytical factors on liquid biopsy in the canine cancer model

While liquid biopsy has potential to transform cancer diagnostics through minimally-invasive detection and monitoring of tumors, the impact of preanalytical factors such as the timing and anatomical location of blood draw is not well understood. To address this gap, we leveraged pet dogs with spontaneous cancer as a model system, as their compressed disease timeline facilitates rapid diagnostic benchmarking. Key liquid biopsy metrics from dogs were consistent with existing reports from human patients. The tumor content of samples was higher from venipuncture sites closer to the tumor and from a central vein. Metrics also differed between lymphoma and non-hematopoietic cancers, urging cancer-type-specific interpretation. Liquid biopsy was highly sensitive to disease status, with changes identified soon after post chemotherapy administration, and trends of increased tumor fraction and other metrics observed prior to clinical relapse in dogs with lymphoma or osteosarcoma. These data support the utility of pet dogs with cancer as a relevant system for advancing liquid biopsy platforms.

genomics↗

bioRxiv2022

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

BackgroundCanine hemangiosarcoma (HSA) is an aggressive cancer of endothelial cells associated with short survival times. Understanding the genomic landscape of HSA is critical to developing more effective therapeutic strategies. ObjectivesTo determine the relationships between genomic and clinical features including treatment and outcome in canine splenic HSA. Animals109 dogs with primary splenic HSA treated by splenectomy that had tumor sequencing via the FidoCure(R) Precision Medicine Platform targeted sequencing panel. MethodsPatient signalment, weight, metastasis at diagnosis, treatment, and survival time were retrospectively evaluated. The incidence of genomic alterations in individual genes and their relationship to patient variables and outcome were assessed. ResultsSomatic mutations in TP53 (n = 45), NRAS (n = 20), and PIK3CA (n = 19) were most common. Survival was associated with metastases at diagnosis, germline variants in SETD2 and NOTCH1, and nominally with breed. Age at diagnosis was associated with NRAS mutations and breed. TP53 and PIK3CA mutations were found in larger dogs, germline SETD2 variants in smaller dogs. Doxorubicin (DOX) treatment did not significantly improve survival time, while targeted therapies had a significant early survival benefit. Conclusions and clinical importanceDOX treatment may provide limited clinical benefit for dogs with splenic HSA, while targeted therapy may provide early survival benefit. Genetic signatures associated with splenic HSA may be useful in guiding targeted therapy to improve outcomes. Germline variants, age, size, and breed may be useful prognostic factors and provide insight into the genomic landscape of the tumor.

genomics↗

bioRxiv2019

Genomic analysis reveals shared genes and pathways in human and canine angiosarcoma

Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with high fatality and few effective treatment options. It is both rare and heterogenous, making large, well powered genomic studies nearly impossible. In dogs, angiosarcoma is common, with breeds like the golden retriever carrying heritable genetic factors that put them at very high risk. If the clinical similarity of canine and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine angiosarcoma via whole exome sequencing (47 golden retriever angiosarcomas) and RNA sequencing (74 angiosarcomas from multiple breeds). The predominant mutational signature was the age-associated deamination of cytosine to thymine, and somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). We compared the canine data to human data recently released by The Angiosarcoma Project, and found the same genes and many of the same pathways significantly enriched for somatic mutations, most notably protein kinases, glycoproteins, fibronectin Type III domains, EGF-like domains, and cell adhesion proteins such as cadherins. As in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. Canine angiosarcoma closely models human angiosarcoma on a genomic level, and is a powerful tool for investigating the pathogenesis of this devastating disease.

genomics↗