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Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma

Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that shares many similarities with spontaneously occurring hemangiosarcoma (HSA) in dogs and cats. To investigate the genetic suitability of HSA as a model for AS, we sequenced ∼1000 cancer genes in 41 cases of H...

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Autores principales: Wong, Kim, Ludwig, Latasha, Krijgsman, Oscar, Adams, David J., Wood, Geoffrey A., van der Weyden, Louise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319545/
https://www.ncbi.nlm.nih.gov/pubmed/34296746
http://dx.doi.org/10.1242/dmm.049044
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author Wong, Kim
Ludwig, Latasha
Krijgsman, Oscar
Adams, David J.
Wood, Geoffrey A.
van der Weyden, Louise
author_facet Wong, Kim
Ludwig, Latasha
Krijgsman, Oscar
Adams, David J.
Wood, Geoffrey A.
van der Weyden, Louise
author_sort Wong, Kim
collection PubMed
description Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that shares many similarities with spontaneously occurring hemangiosarcoma (HSA) in dogs and cats. To investigate the genetic suitability of HSA as a model for AS, we sequenced ∼1000 cancer genes in 41 cases of HSA and matched germline tissue: 15 canine visceral HSAs, 13 canine skin HSAs and 13 feline skin HSAs. Analysis of visceral HSAs from dogs presenting with concurrent splenic and cardiac neoplasms showed that the tumors were not independent primaries, consistent with the highly metastatic nature of HSA. Comparison of HSA to AS revealed that several driver genes were recurrently mutated in both species, such as TP53, PIK3CA, ATRX, GRIN2A and LRP1B. Similar to AS, a UV mutational signature was found in a subset of canine cutaneous HSAs and both species show differing mutational profiles between tissue sites. Our characterization of canine and feline HSA demonstrates many important parallels to AS and provides hope that future studies on these cancers will benefit of all three species.
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spelling pubmed-83195452021-07-29 Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma Wong, Kim Ludwig, Latasha Krijgsman, Oscar Adams, David J. Wood, Geoffrey A. van der Weyden, Louise Dis Model Mech Research Article Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that shares many similarities with spontaneously occurring hemangiosarcoma (HSA) in dogs and cats. To investigate the genetic suitability of HSA as a model for AS, we sequenced ∼1000 cancer genes in 41 cases of HSA and matched germline tissue: 15 canine visceral HSAs, 13 canine skin HSAs and 13 feline skin HSAs. Analysis of visceral HSAs from dogs presenting with concurrent splenic and cardiac neoplasms showed that the tumors were not independent primaries, consistent with the highly metastatic nature of HSA. Comparison of HSA to AS revealed that several driver genes were recurrently mutated in both species, such as TP53, PIK3CA, ATRX, GRIN2A and LRP1B. Similar to AS, a UV mutational signature was found in a subset of canine cutaneous HSAs and both species show differing mutational profiles between tissue sites. Our characterization of canine and feline HSA demonstrates many important parallels to AS and provides hope that future studies on these cancers will benefit of all three species. The Company of Biologists Ltd 2021-07-23 /pmc/articles/PMC8319545/ /pubmed/34296746 http://dx.doi.org/10.1242/dmm.049044 Text en © 2021. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Wong, Kim
Ludwig, Latasha
Krijgsman, Oscar
Adams, David J.
Wood, Geoffrey A.
van der Weyden, Louise
Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
title Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
title_full Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
title_fullStr Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
title_full_unstemmed Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
title_short Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
title_sort comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319545/
https://www.ncbi.nlm.nih.gov/pubmed/34296746
http://dx.doi.org/10.1242/dmm.049044
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