Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions
Abstract Comparative studies of naturally occurring canine cancers have provided new insight into many areas of cancer research. Development and validation of circulating tumor DNA (ctDNA) analysis in pet dogs can help address diagnostic needs in veterinary as well as human oncology. Dogs have high...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-09716-6 |
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| author | Patricia Filippsen Favaro Samuel D. Stewart Bradon R. McDonald Jacob Cawley Tania Contente-Cuomo Shukmei Wong William P. D. Hendricks Jeffrey M. Trent Chand Khanna Muhammed Murtaza |
| author_facet | Patricia Filippsen Favaro Samuel D. Stewart Bradon R. McDonald Jacob Cawley Tania Contente-Cuomo Shukmei Wong William P. D. Hendricks Jeffrey M. Trent Chand Khanna Muhammed Murtaza |
| author_sort | Patricia Filippsen Favaro |
| collection | DOAJ |
| description | Abstract Comparative studies of naturally occurring canine cancers have provided new insight into many areas of cancer research. Development and validation of circulating tumor DNA (ctDNA) analysis in pet dogs can help address diagnostic needs in veterinary as well as human oncology. Dogs have high incidence of naturally occurring spontaneous cancers, demonstrate molecular heterogeneity and clonal evolution during therapy, allow serial sampling of blood from the same individuals during the course of disease progression, and have relatively compressed intervals for disease progression amenable to longitudinal studies. Here, we present a feasibility study of ctDNA analysis performed in 48 dogs including healthy dogs and dogs with either benign splenic lesions or malignant splenic tumors (hemangiosarcoma) using shallow whole genome sequencing (sWGS) of cell-free DNA. To enable detection and quantification of ctDNA using sWGS, we adapted two informatic approaches and compared their performance for the canine genome. At the time of initial clinical presentation, mean ctDNA fraction in dogs with malignant splenic tumors was 11.2%, significantly higher than dogs with benign lesions (3.2%; p = 0.001). ctDNA fraction was 14.3% and 9.0% in dogs with metastatic and localized disease, respectively (p = 0.227). In dogs treated with surgical resection of malignant tumors, mean ctDNA fraction decreased from 11.0% prior to resection to 7.9% post-resection (p = 0.047 for comparison of paired samples). Our results demonstrate that ctDNA analysis is feasible in dogs with hemangiosarcoma using a cost-effective approach such as sWGS. Additional studies are needed to validate these findings, and determine the role of ctDNA to assess burden of disease and treatment response in dogs with cancer. |
| first_indexed | 2024-04-14T08:29:31Z |
| format | Article |
| id | doaj.art-cc29ebdfe079466b908868b23dd9fa40 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-14T08:29:31Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-cc29ebdfe079466b908868b23dd9fa402022-12-22T02:03:58ZengNature PortfolioScientific Reports2045-23222022-04-0112111010.1038/s41598-022-09716-6Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesionsPatricia Filippsen Favaro0Samuel D. Stewart1Bradon R. McDonald2Jacob Cawley3Tania Contente-Cuomo4Shukmei Wong5William P. D. Hendricks6Jeffrey M. Trent7Chand Khanna8Muhammed Murtaza9Translational Genomics Research Institute (TGen)Ethos Veterinary HealthTranslational Genomics Research Institute (TGen)Ethos Veterinary HealthTranslational Genomics Research Institute (TGen)Translational Genomics Research Institute (TGen)Translational Genomics Research Institute (TGen)Translational Genomics Research Institute (TGen)Ethos Veterinary HealthTranslational Genomics Research Institute (TGen)Abstract Comparative studies of naturally occurring canine cancers have provided new insight into many areas of cancer research. Development and validation of circulating tumor DNA (ctDNA) analysis in pet dogs can help address diagnostic needs in veterinary as well as human oncology. Dogs have high incidence of naturally occurring spontaneous cancers, demonstrate molecular heterogeneity and clonal evolution during therapy, allow serial sampling of blood from the same individuals during the course of disease progression, and have relatively compressed intervals for disease progression amenable to longitudinal studies. Here, we present a feasibility study of ctDNA analysis performed in 48 dogs including healthy dogs and dogs with either benign splenic lesions or malignant splenic tumors (hemangiosarcoma) using shallow whole genome sequencing (sWGS) of cell-free DNA. To enable detection and quantification of ctDNA using sWGS, we adapted two informatic approaches and compared their performance for the canine genome. At the time of initial clinical presentation, mean ctDNA fraction in dogs with malignant splenic tumors was 11.2%, significantly higher than dogs with benign lesions (3.2%; p = 0.001). ctDNA fraction was 14.3% and 9.0% in dogs with metastatic and localized disease, respectively (p = 0.227). In dogs treated with surgical resection of malignant tumors, mean ctDNA fraction decreased from 11.0% prior to resection to 7.9% post-resection (p = 0.047 for comparison of paired samples). Our results demonstrate that ctDNA analysis is feasible in dogs with hemangiosarcoma using a cost-effective approach such as sWGS. Additional studies are needed to validate these findings, and determine the role of ctDNA to assess burden of disease and treatment response in dogs with cancer.https://doi.org/10.1038/s41598-022-09716-6 |
| spellingShingle | Patricia Filippsen Favaro Samuel D. Stewart Bradon R. McDonald Jacob Cawley Tania Contente-Cuomo Shukmei Wong William P. D. Hendricks Jeffrey M. Trent Chand Khanna Muhammed Murtaza Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions Scientific Reports |
| title | Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions |
| title_full | Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions |
| title_fullStr | Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions |
| title_full_unstemmed | Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions |
| title_short | Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions |
| title_sort | feasibility of circulating tumor dna analysis in dogs with naturally occurring malignant and benign splenic lesions |
| url | https://doi.org/10.1038/s41598-022-09716-6 |
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