Journal article
Molecular Alterations in Dog Pheochromocytomas and Paragangliomas
Cancers, Vol.11(5)
2019
Abstract
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.
Details
- Title
- Molecular Alterations in Dog Pheochromocytomas and Paragangliomas
- Authors/Creators
- E. Korpershoek (Author/Creator) - Erasmus MC Cancer InstituteD.A.E.R. Dieduksman (Author/Creator) - Erasmus MC Cancer InstituteG.C.M. Grinwis (Author/Creator) - Utrecht UniversityM.J. Day (Author/Creator) - Murdoch UniversityC.E. Reusch (Author/Creator) - University of ZurichM. Hilbe (Author/Creator) - University of ZurichF. Fracassi (Author/Creator) - University of BolognaN.M.G. Krol (Author/Creator) - Erasmus MC Cancer InstituteA.G. Uitterlinden (Author/Creator) - Genetic Laboratory, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands. a.g.uitterlinden@erasmusmc.nl.A. de Klein (Author/Creator) - Erasmus MCB. Eussen (Author/Creator) - Erasmus University RotterdamH. Stoop (Author/Creator) - Erasmus MC Cancer InstituteR.R. de Krijger (Author/Creator) - Princess Máxima CenterS. Galac (Author/Creator) - Utrecht UniversityW.N.M. Dinjens (Author/Creator) - Erasmus MC Cancer Institute
- Publication Details
- Cancers, Vol.11(5)
- Publisher
- MDPI AG
- Identifiers
- 991005541152407891
- Copyright
- © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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