Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783426541704708096
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
work_keys_str_mv AT korpershoekesther molecularalterationsindogpheochromocytomasandparagangliomas
AT dieduksmandaphneaer molecularalterationsindogpheochromocytomasandparagangliomas
AT grinwisguycm molecularalterationsindogpheochromocytomasandparagangliomas
AT daymichaelj molecularalterationsindogpheochromocytomasandparagangliomas
AT reuschclaudiae molecularalterationsindogpheochromocytomasandparagangliomas
AT hilbemonika molecularalterationsindogpheochromocytomasandparagangliomas
AT fracassifederico molecularalterationsindogpheochromocytomasandparagangliomas
AT krolnielsmg molecularalterationsindogpheochromocytomasandparagangliomas
AT uitterlindenandreg molecularalterationsindogpheochromocytomasandparagangliomas
AT dekleinannelies molecularalterationsindogpheochromocytomasandparagangliomas
AT eussenbert molecularalterationsindogpheochromocytomasandparagangliomas
AT stoophans molecularalterationsindogpheochromocytomasandparagangliomas
AT dekrijgerronaldr molecularalterationsindogpheochromocytomasandparagangliomas
AT galacsara molecularalterationsindogpheochromocytomasandparagangliomas
AT dinjenswinandnm molecularalterationsindogpheochromocytomasandparagangliomas