Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds

Evans, Judith; Parker, Heidi G.; Rutteman, Gerard R.; Plassais, Jocelyn; Grinwis, Guy C. M.; Harris, Alex C.; Lana, Susan E.; Ostrander, Elaine A.

doi:10.1371/journal.pgen.1009543

Cited by 16 publications

(15 citation statements)

References 53 publications

(85 reference statements)

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“…The study used flat-coated retrievers that frequently develop a disease of the similar histological and clinical features to histiocytic sarcoma. The PI3K pathway gene PIK3R6 on canine chromosome 5 was observed strongly associated to histiocytic sarcoma in dogs, and upregulation of TNFIAP6 in chromosome 19 is considered a risk factor as well (22). The research also shows the potential of dog breeds as excellent subjects for omics analysis, for they have perfect hereditary consistency after years of artificial selection.…”

Section: Genomics and Transcriptomicsmentioning

confidence: 77%

Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets

Zou

Sun

et al. 2022

Front. Oncol.

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Sarcomas are rare, heterogeneous mesenchymal neoplasms with various subtypes, each exhibiting unique genetic characteristics. Although studies have been conducted to improve the treatment for sarcomas, the specific development from normal somatic cells to sarcoma cells is still unclear and needs further research. The diagnosis of sarcomas depends heavily on the pathological examination, which is yet a difficult work and requires expert analysis. Advanced treatment like precise medicine optimizes the efficacy of treatment and the prognosis of sarcoma patients, yet, in sarcomas, more studies should be done to put such methods in clinical practice. The revolution of advanced technology has pushed the multi-omics approach to the front, and more could be learnt in sarcomas with such methods. Multi-omics combines the character of each omics techniques, analyzes the mechanism of tumor cells from different levels, which makes up for the shortage of single-omics, and gives us an integrated picture of bioactivities inside tumor cells. Multi-omics research of sarcomas has reached appreciable progress in recent years, leading to a better understanding of the mutation, proliferation, and metastasis of sarcomas. With the help of multi-omics approach, novel biomarkers were found, with promising effects in improving the process of diagnosis, prognosis anticipation, and treatment decision. By analyzing large amounts of biological features, subtype clustering could be done in a better precision, which may be useful in the clinical procedure. In this review, we summarized recent discoveries using multi-omics approach in sarcomas, discussed their merits and challenges, and concluded with future perspectives of the sarcoma research.

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Section: Genomics and Transcriptomicsmentioning

confidence: 77%

Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets

Zou

Sun

et al. 2022

Front. Oncol.

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“…In this context, it is noteworthy that a shared region of the canine genome has been found to be significantly associated with B-cell lymphomas, hemangiosarcomas, and other blood derived tumors in various breeds of dogs belonging to distinct genetic clades (51–53). This finding highlights the intriguing possibility of a molecular connection between these seemingly distinct tumors, suggesting that disruptions in hematopoiesis and cellular reprogramming may contribute to their development (54).…”

Section: Discussionmentioning

confidence: 99%

Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Kim

Schulte

Sarver

et al. 2021

Preprint

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Hemangiosarcoma and angiosarcoma are soft tissue sarcomas of malignant blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs that support the niche, enabling progression of canine hemangiosarcoma and human angiosarcoma. Here, we show that the transcriptional landscape of canine hemangiosarcoma and human angiosarcoma included comparable angiogenic and inflammatory programs. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells, a trait that was not observed in xenografts from canine osteosarcoma and lymphoma. In some cases, the xenografted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. We did not uncover a definitive transmissible etiology, but our data indicate that transcriptional programs of hemangiosarcoma cells resemble those of hematopoietic nurse cells, and these malignant cells support expansion and differentiation of human hematopoietic progenitors. We conclude that canine hemangiosarcoma, and possibly human angiosarcoma, originate from nurse cells that make up the stromal bone marrow niche, and that these cells may also support the growth of hematopoietic tumors.

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“…Major attention has been paid to veterinary oncology, not least because of the comparative insights with humans it provides. In particular, neoplastic diseases investigated through omics technologies are hematopoietic neoplasms [79][80][81][82], mammary tumors [83][84][85], oral neoplasms [86], neuroendocrine tumors [87], and melanocytic tumors [73,88]. Further disorders addressed by omics approaches include cardiopathies [89][90][91], endocrinopathies such as hyperadrenocorticism [92] and diabetes mellitus [93,94], hepatopathies [95][96][97], chronic kidney disease [98,99], and inflammatory/infectious diseases(i.e., sepsis [100], pyometra [101], and vector-borne diseases [102,103]).…”

Section: Integrative Multiomics Approaches In Veterinary Medicinementioning

confidence: 99%

Omics Technologies in Veterinary Medicine: Literature Review and Perspectives in Transfusion Medicine

Miglio,

Cremonini,

Leonardi

et al. 2023

Transfus Med Hemother

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Background: Omics technologies represent a new analytical approach that allows a full cellular readout through the simultaneous analysis of thousands of molecules. The application of such technologies represents a flourishing field of research in human medicine, especially in transfusion medicine, while their application in veterinary medicine still needs to be developed. Summary: Omics technologies, especially proteomics, metabolomics, and lipidomics, are currently applied in several fields of human medicine. In transfusion medicine, the creation and integration of multiomics datasets have uncovered intricate molecular pathways occurring within blood bags during storage. In particular, the research has been directed toward the study of storage lesions (SLs), i.e., those biochemical and structural changes that red blood cells (RBCs) undergo during hypothermic storage, their causes, and the development of new strategies to prevent them. However, due to their challenges to perform and high costs, these technologies are hardly accessible to veterinary research, where their application dates back only to the last few years and thus a great deal of progress still needs to be made. As regards veterinary medicine, there are only a few studies that have focused mainly on fields such as oncology, nutrition, cardiology, and nephrology. Other studies have suggested omics datasets that provide important insights for future comparative investigations between human and nonhuman species. Regarding the study of storage lesions and, more generally, the veterinary transfusion field, there is a marked lack of available omics data and results with relevance for clinical practice. Key Messages: The use of omics technologies in human medicine is well established and has led to promising results in blood transfusion and related practices knowledge. Transfusion practice is a burgeoning field in veterinary medicine, but, to date, there are no species-specific procedures and techniques for the collection and storage of blood units and those validated in the human species are univocally pursued. Multiomics analysis of the species-specific RBCs’ biological characteristics could provide promising results both from a comparative perspective, by increasing our understanding of species suitable to be used as animal models, and in a strictly veterinary view, by contributing to the development of animal-targeted procedures.

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Multi-omics approach identifies germline regulatory variants associated with hematopoietic malignancies in retriever dog breeds

Cited by 16 publications

References 53 publications

Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets

Application of Multi-Omics Approach in Sarcomas: A Tool for Studying Mechanism, Biomarkers, and Therapeutic Targets

Hemangiosarcoma Cells Promote Conserved Host-Derived Hematopoietic Expansion

Omics Technologies in Veterinary Medicine: Literature Review and Perspectives in Transfusion Medicine

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