Molecular Alterations in Dog Pheochromocytomas and Paragangliomas
Alterações moleculares em feocromocitomas e paragangliomas de cães
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, AndréG. Uitterlinden, Annelies de Klein, Bert Eussen, Hans Stoop, Ronald R. de Krijger, Sara Galac, Winand N. M. Dinjens
Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit Band D (SDHBandSDHD) 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; SDHBp.Arg38Gln (n=1) and SDHDp.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 humanPPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways.
dog; pheochromocytoma; paraganglioma;SDHB;SDHD; mutation; chromosomalalteration; comparative genomics
cão; feocromocitoma; paraganglioma; SDHB; SDHD; mutação; alteração cromossômica; genômica comparativa