Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.

<h4>Background</h4>The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of h...

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Autores principales: Kim M Boerkamp, Marieke van der Kooij, Frank G van Steenbeek, Monique E van Wolferen, Marian J A Groot Koerkamp, Dik van Leenen, Guy C M Grinwis, Louis C Penning, Erik A C Wiemer, Gerard R Rutteman
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/cb03fb412bee43de96f6241999709856
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spelling oai:doaj.org-article:cb03fb412bee43de96f62419997098562021-11-18T09:01:37ZGene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.1932-620310.1371/journal.pone.0071094https://doaj.org/article/cb03fb412bee43de96f62419997098562013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936488/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed.<h4>Methods</h4>Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses.<h4>Results</h4>QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process.<h4>Conclusions</h4>This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.Kim M BoerkampMarieke van der KooijFrank G van SteenbeekMonique E van WolferenMarian J A Groot KoerkampDik van LeenenGuy C M GrinwisLouis C PenningErik A C WiemerGerard R RuttemanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71094 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kim M Boerkamp
Marieke van der Kooij
Frank G van Steenbeek
Monique E van Wolferen
Marian J A Groot Koerkamp
Dik van Leenen
Guy C M Grinwis
Louis C Penning
Erik A C Wiemer
Gerard R Rutteman
Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
description <h4>Background</h4>The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors have value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed.<h4>Methods</h4>Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses.<h4>Results</h4>QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process.<h4>Conclusions</h4>This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Exploration of the downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.
format article
author Kim M Boerkamp
Marieke van der Kooij
Frank G van Steenbeek
Monique E van Wolferen
Marian J A Groot Koerkamp
Dik van Leenen
Guy C M Grinwis
Louis C Penning
Erik A C Wiemer
Gerard R Rutteman
author_facet Kim M Boerkamp
Marieke van der Kooij
Frank G van Steenbeek
Monique E van Wolferen
Marian J A Groot Koerkamp
Dik van Leenen
Guy C M Grinwis
Louis C Penning
Erik A C Wiemer
Gerard R Rutteman
author_sort Kim M Boerkamp
title Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
title_short Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
title_full Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
title_fullStr Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
title_full_unstemmed Gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
title_sort gene expression profiling of histiocytic sarcomas in a canine model: the predisposed flatcoated retriever dog.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/cb03fb412bee43de96f6241999709856
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