title: Succinate dehydrogenase subunit D and succinate dehydrogenase subunit B mutation analysis in canine phaeochromocytoma and paraganglioma.
abstract: Phaeochromocytomas (PCs) are tumours of the adrenal medulla chromaffin cells. Paragangliomas (PGLs) arise in sympathetic ganglia (previously called extra-adrenal PCs) or in non-chromaffin parasympathetic ganglia cells that are usually non-secretory. Parenchymal cells from these tumours have a common embryological origin from neural crest ectoderm. Several case series of canine PCs and PGLs have been published and a link between the increased incidence of chemoreceptor neoplasia in brachycephalic dog breeds and chronic hypoxia has been postulated. A similar link to hypoxia in man led to the identification of germline heterozygous mutations in the gene encoding succinate dehydrogenase subunit D (SDHD) and subsequently SDHA, SDHB and SDHC in similar tumours. We investigated canine PCs (n = 6) and PGLs (n = 2) for SDHD and SDHB mutations and in one PGL found a somatic SDHD mutation c.365A>G (p.Lys122Arg) in exon 4, which was not present in normal tissue from this brachycephalic dog. Two PCs were heterozygous for both c.365A>G (p.Lys122Arg) mutation and an exon 3 silent variant c.291G>A. We also identified the heterozygous SDHB exon 2 mutation c.113G>A (p.Arg38Gln) in a PC. These results illustrate that genetic mutations may underlie tumourigenesis in canine PCs and PGLs. The spontaneous nature of these canine diseases and possible association of PGLs with hypoxia in brachycephalic breeds may make them an attractive model for studying the corresponding human tumours.
authors.affiliation: Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA. Electronic address: dholt@vet.upenn.edu.
authors.forename: D E
authors.initials: DE
authors.lastname: Holt
authors.affiliation: Department of Clinical Studies, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Henthorn
authors.affiliation: Bill Walsh Translational Cancer Research Laboratory, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia.
authors.forename: V M
authors.initials: VM
authors.lastname: Howell
authors.affiliation: Cancer Genetics Laboratory, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia.
authors.forename: B G
authors.initials: BG
authors.lastname: Robinson
authors.affiliation: Cancer Genetics Laboratory, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia.
authors.forename: D E
authors.initials: DE
authors.lastname: Benn
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000662:veterinary*; D000818:Animals; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics / Q000662:veterinary; D010673:Pheochromocytoma / Q000235:genetics / Q000662:veterinary*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase
keywords: SDHD/B gene; dog; paraganglioma; phaeochromocytoma