Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs
Age-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been us...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/10/7/455 |
| _version_ | 1797587219086573568 |
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| author | Kristina M. Kruglyak Allison L. O’Kell Todd A. Cohen Maggie A. Marshall Carlos A. Ruiz-Perez Francesco Marass John A. Tynan Susan C. Hicks Katherine M. Lytle Ashley Phelps-Dunn Gina Brandstetter Chelsea D. Warren Lauren R. DiMarzio Michelle C. Rosentel Lilian K. Wong Lisa M. McLennan Jill M. Rafalko Daniel S. Grosu Jason Chibuk Ilya Chorny Angela L. McCleary-Wheeler Andi Flory Dana W. Y. Tsui |
| author_facet | Kristina M. Kruglyak Allison L. O’Kell Todd A. Cohen Maggie A. Marshall Carlos A. Ruiz-Perez Francesco Marass John A. Tynan Susan C. Hicks Katherine M. Lytle Ashley Phelps-Dunn Gina Brandstetter Chelsea D. Warren Lauren R. DiMarzio Michelle C. Rosentel Lilian K. Wong Lisa M. McLennan Jill M. Rafalko Daniel S. Grosu Jason Chibuk Ilya Chorny Angela L. McCleary-Wheeler Andi Flory Dana W. Y. Tsui |
| author_sort | Kristina M. Kruglyak |
| collection | DOAJ |
| description | Age-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been used to study the genomic profiles of blood samples from thousands of canine patients since 2021. In this study, 4870 client-owned dogs with and without a diagnosis or suspicion of cancer underwent liquid biopsy testing by this method. Copy number variants detected exclusively in genomic DNA derived from white blood cells (WBC gDNA-specific CNVs) were observed in 126 dogs (2.6%; 95% CI: 2.2–3.1); these copy number variants were absent from matched plasma cell-free DNA, and from tumor tissue in dogs with concurrent cancer. These findings were more common in older dogs and were persistent in WBC gDNA in over 70% of patients, with little to no change in the amplitude of the signal across longitudinal samples. Many of these alterations were observed at recurrent locations in the genome across subjects; the most common finding was a partial loss on CFA25, typically accompanied by a partial gain on the same chromosome. These early findings suggest that age-related somatic alterations may be present at an appreciable frequency in the general canine population. Further research is needed to determine the clinical significance of these findings. |
| first_indexed | 2024-03-11T00:34:02Z |
| format | Article |
| id | doaj.art-3a9289a6ca7a4026b2f0d1f4db2b7333 |
| institution | Directory Open Access Journal |
| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-11T00:34:02Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj.art-3a9289a6ca7a4026b2f0d1f4db2b73332023-11-18T21:42:48ZengMDPI AGVeterinary Sciences2306-73812023-07-0110745510.3390/vetsci10070455Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 DogsKristina M. Kruglyak0Allison L. O’Kell1Todd A. Cohen2Maggie A. Marshall3Carlos A. Ruiz-Perez4Francesco Marass5John A. Tynan6Susan C. Hicks7Katherine M. Lytle8Ashley Phelps-Dunn9Gina Brandstetter10Chelsea D. Warren11Lauren R. DiMarzio12Michelle C. Rosentel13Lilian K. Wong14Lisa M. McLennan15Jill M. Rafalko16Daniel S. Grosu17Jason Chibuk18Ilya Chorny19Angela L. McCleary-Wheeler20Andi Flory21Dana W. Y. Tsui22Information Technology, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAInformation Technology, PetDx, La Jolla, CA 92037, USAInformation Technology, PetDx, La Jolla, CA 92037, USAInformation Technology, PetDx, La Jolla, CA 92037, USAResearch Programs, PetDx, La Jolla, CA 92037, USAAnalytical Production, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAResearch Programs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAInformation Technology, PetDx, La Jolla, CA 92037, USAResearch Programs, PetDx, La Jolla, CA 92037, USAMedical & Clinical Affairs, PetDx, La Jolla, CA 92037, USAResearch Programs, PetDx, La Jolla, CA 92037, USAAge-related somatic genomic alterations in hematopoietic cell lines have been well characterized in humans; however, this phenomenon has not been well studied in other species. Next-generation sequencing-based liquid biopsy testing for cancer detection was recently developed for dogs and has been used to study the genomic profiles of blood samples from thousands of canine patients since 2021. In this study, 4870 client-owned dogs with and without a diagnosis or suspicion of cancer underwent liquid biopsy testing by this method. Copy number variants detected exclusively in genomic DNA derived from white blood cells (WBC gDNA-specific CNVs) were observed in 126 dogs (2.6%; 95% CI: 2.2–3.1); these copy number variants were absent from matched plasma cell-free DNA, and from tumor tissue in dogs with concurrent cancer. These findings were more common in older dogs and were persistent in WBC gDNA in over 70% of patients, with little to no change in the amplitude of the signal across longitudinal samples. Many of these alterations were observed at recurrent locations in the genome across subjects; the most common finding was a partial loss on CFA25, typically accompanied by a partial gain on the same chromosome. These early findings suggest that age-related somatic alterations may be present at an appreciable frequency in the general canine population. Further research is needed to determine the clinical significance of these findings.https://www.mdpi.com/2306-7381/10/7/455clonal hematopoiesis of indeterminate potential (CHIP)age-related clonal hematopoiesis (ARCH)copy number variant (CNV)next-generation sequencing (NGS)somaticgermline |
| spellingShingle | Kristina M. Kruglyak Allison L. O’Kell Todd A. Cohen Maggie A. Marshall Carlos A. Ruiz-Perez Francesco Marass John A. Tynan Susan C. Hicks Katherine M. Lytle Ashley Phelps-Dunn Gina Brandstetter Chelsea D. Warren Lauren R. DiMarzio Michelle C. Rosentel Lilian K. Wong Lisa M. McLennan Jill M. Rafalko Daniel S. Grosu Jason Chibuk Ilya Chorny Angela L. McCleary-Wheeler Andi Flory Dana W. Y. Tsui Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs Veterinary Sciences clonal hematopoiesis of indeterminate potential (CHIP) age-related clonal hematopoiesis (ARCH) copy number variant (CNV) next-generation sequencing (NGS) somatic germline |
| title | Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs |
| title_full | Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs |
| title_fullStr | Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs |
| title_full_unstemmed | Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs |
| title_short | Detection of Age-Related Somatic Alterations in Canine Blood Using Next-Generation Sequencing-Based Liquid Biopsy: An Analysis of over 4800 Dogs |
| title_sort | detection of age related somatic alterations in canine blood using next generation sequencing based liquid biopsy an analysis of over 4800 dogs |
| topic | clonal hematopoiesis of indeterminate potential (CHIP) age-related clonal hematopoiesis (ARCH) copy number variant (CNV) next-generation sequencing (NGS) somatic germline |
| url | https://www.mdpi.com/2306-7381/10/7/455 |
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