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Molecular Alterations in Dog Pheochromocytomas and Paragangliomas
Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563419/ https://www.ncbi.nlm.nih.gov/pubmed/31052272 http://dx.doi.org/10.3390/cancers11050607 |
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author | Korpershoek, Esther Dieduksman, Daphne A. E. R. Grinwis, Guy C. M. Day, Michael J. Reusch, Claudia E. Hilbe, Monika Fracassi, Federico Krol, Niels M. G. Uitterlinden, André G. de Klein, Annelies Eussen, Bert Stoop, Hans de Krijger, Ronald R. Galac, Sara Dinjens, Winand N. M. |
author_facet | Korpershoek, Esther Dieduksman, Daphne A. E. R. Grinwis, Guy C. M. Day, Michael J. Reusch, Claudia E. Hilbe, Monika Fracassi, Federico Krol, Niels M. G. Uitterlinden, André G. de Klein, Annelies Eussen, Bert Stoop, Hans de Krijger, Ronald R. Galac, Sara Dinjens, Winand N. M. |
author_sort | Korpershoek, Esther |
collection | PubMed |
description | Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways. |
format | Online Article Text |
id | pubmed-6563419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65634192019-06-17 Molecular Alterations in Dog Pheochromocytomas and Paragangliomas Korpershoek, Esther Dieduksman, Daphne A. E. R. Grinwis, Guy C. M. Day, Michael J. Reusch, Claudia E. Hilbe, Monika Fracassi, Federico Krol, Niels M. G. Uitterlinden, André G. de Klein, Annelies Eussen, Bert Stoop, Hans de Krijger, Ronald R. Galac, Sara Dinjens, Winand N. M. Cancers (Basel) Article Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways. MDPI 2019-04-30 /pmc/articles/PMC6563419/ /pubmed/31052272 http://dx.doi.org/10.3390/cancers11050607 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Korpershoek, Esther Dieduksman, Daphne A. E. R. Grinwis, Guy C. M. Day, Michael J. Reusch, Claudia E. Hilbe, Monika Fracassi, Federico Krol, Niels M. G. Uitterlinden, André G. de Klein, Annelies Eussen, Bert Stoop, Hans de Krijger, Ronald R. Galac, Sara Dinjens, Winand N. M. Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title | Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title_full | Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title_fullStr | Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title_full_unstemmed | Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title_short | Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title_sort | molecular alterations in dog pheochromocytomas and paragangliomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563419/ https://www.ncbi.nlm.nih.gov/pubmed/31052272 http://dx.doi.org/10.3390/cancers11050607 |
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