Molecular Alterations in Dog Pheochromocytomas and Paragangliomas
Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (<i>SDHB</i> and <i>SDHD</i>) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs mig...
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doaj-cceed9b6eb114238b93e8d720013c00b2020-11-25T01:27:27ZengMDPI AGCancers2072-66942019-04-0111560710.3390/cancers11050607cancers11050607Molecular Alterations in Dog Pheochromocytomas and ParagangliomasEsther Korpershoek0Daphne A. E. R. Dieduksman1Guy C. M. Grinwis2Michael J. Day3Claudia E. Reusch4Monika Hilbe5Federico Fracassi6Niels M. G. Krol7André G. Uitterlinden8Annelies de Klein9Bert Eussen10Hans Stoop11Ronald R. de Krijger12Sara Galac13Winand N. M. Dinjens14Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The NetherlandsSchool of Veterinary and Life Sciences, Murdoch University, Murdoch 6150, WA, AustraliaClinic for Small Animal Internal Medicine, University of Zurich, 8057 Zurich, SwitzerlandInstitute of Veterinary Pathology, University of Zurich, 8057 Zurich, SwitzerlandDepartment of Veterinary Medical Science, University of Bologna, 40064 Ozzano dell’Emilia, ItalyDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The NetherlandsGenetic Laboratory, Erasmus MC University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Pathology University Medical Center/Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The NetherlandsDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The NetherlandsDepartment of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The NetherlandsRecently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (<i>SDHB</i> and <i>SDHD</i>) 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 <i>SDHB</i> and <i>SDHD</i> 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; <i>SDHB</i> p.Arg38Gln (<i>n</i> = 1) and <i>SDHD</i> p.Lys122Arg (<i>n</i> = 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.https://www.mdpi.com/2072-6694/11/5/607dogpheochromocytomaparaganglioma<i>SDHB</i><i>SDHD</i>mutationchromosomal alterationcomparative genomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Esther Korpershoek Daphne A. E. R. Dieduksman Guy C. M. Grinwis Michael J. Day Claudia E. Reusch Monika Hilbe Federico Fracassi Niels M. G. Krol André G. Uitterlinden Annelies de Klein Bert Eussen Hans Stoop Ronald R. de Krijger Sara Galac Winand N. M. Dinjens |
spellingShingle |
Esther Korpershoek Daphne A. E. R. Dieduksman Guy C. M. Grinwis Michael J. Day Claudia E. Reusch Monika Hilbe Federico Fracassi Niels M. G. Krol André G. Uitterlinden Annelies de Klein Bert Eussen Hans Stoop Ronald R. de Krijger Sara Galac Winand N. M. Dinjens Molecular Alterations in Dog Pheochromocytomas and Paragangliomas Cancers dog pheochromocytoma paraganglioma <i>SDHB</i> <i>SDHD</i> mutation chromosomal alteration comparative genomics |
author_facet |
Esther Korpershoek Daphne A. E. R. Dieduksman Guy C. M. Grinwis Michael J. Day Claudia E. Reusch Monika Hilbe Federico Fracassi Niels M. G. Krol André G. Uitterlinden Annelies de Klein Bert Eussen Hans Stoop Ronald R. de Krijger Sara Galac Winand N. M. Dinjens |
author_sort |
Esther Korpershoek |
title |
Molecular Alterations in Dog Pheochromocytomas and Paragangliomas |
title_short |
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_sort |
molecular alterations in dog pheochromocytomas and paragangliomas |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-04-01 |
description |
Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (<i>SDHB</i> and <i>SDHD</i>) 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 <i>SDHB</i> and <i>SDHD</i> 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; <i>SDHB</i> p.Arg38Gln (<i>n</i> = 1) and <i>SDHD</i> p.Lys122Arg (<i>n</i> = 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. |
topic |
dog pheochromocytoma paraganglioma <i>SDHB</i> <i>SDHD</i> mutation chromosomal alteration comparative genomics |
url |
https://www.mdpi.com/2072-6694/11/5/607 |
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