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11. Molecular Alterations in Dog Pheochromocytomas and Paragangliomas

Author

Korpershoek, E., Dieduksman, D.A.E.R., Grinwis, G.C.M., Day, M.J., Reusch, C.E., Hilbe, M., Fracassi, F., Krol, N.M.G., Uitterlinden, A.G., de Klein, A., Eussen, B., Stoop, H., de Krijger, R.R., Galac, S., Dinjens, W.N.M., Korpershoek, E., Dieduksman, D.A.E.R., Grinwis, G.C.M., Day, M.J., Reusch, C.E., Hilbe, M., Fracassi, F., Krol, N.M.G., Uitterlinden, A.G., de Klein, A., Eussen, B., Stoop, H., de Krijger, R.R., Galac, S., and Dinjens, W.N.M.

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.

Published
2019

12. Molecular alterations in dog pheochromocytomas and paragangliomas

Author

Korpershoek, E. (Esther), Dieduksman, D.A.E.R. (Daphne A.E.R.), Grinwis, G.C.M. (Guy C.), Day, M.J. (Michael J.), Reusch, C.E. (Claudia E.), Hilbe, M. (Monika), Fracassi, F. (Federico), Krol, N.M.G. (Niels M. G.), Uitterlinden, A.G. (André), Klein, A. (Annelies) de, Eussen, H.J.F.M.M. (Bert), Stoop, J.A. (Hans), Krijger, R.R. (Ronald) de, Galac, S. (Sara), Dinjens, W.N.M. (Winand), Korpershoek, E. (Esther), Dieduksman, D.A.E.R. (Daphne A.E.R.), Grinwis, G.C.M. (Guy C.), Day, M.J. (Michael J.), Reusch, C.E. (Claudia E.), Hilbe, M. (Monika), Fracassi, F. (Federico), Krol, N.M.G. (Niels M. G.), Uitterlinden, A.G. (André), Klein, A. (Annelies) de, Eussen, H.J.F.M.M. (Bert), Stoop, J.A. (Hans), Krijger, R.R. (Ronald) de, Galac, S. (Sara), and Dinjens, W.N.M. (Winand)

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.

Published
2019
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36. Comparison of Serum Spec fPL™ and 1,2- o-Dilauryl-Rac-Glycero-3-Glutaric Acid-(6′-Methylresorufin) Ester Assay in 60 Cats Using Standardized Assessment of Pancreatic Histology.

Author

Oppliger, S., Hilbe, M., Hartnack, S., Zini, E., Reusch, C.E., and Kook, P.H.

Subjects
PANCREATITIS, CAT diseases, ESTERS, AUTOPSY, INFLAMMATION
Abstract

Background Feline pancreas-specific lipase (Spec fPL) is considered a useful test for the antemortem diagnosis of pancreatitis in cats. A recent study found good agreement between the results of the Spec fPL and catalytic 1,2- o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester ( DGGR) lipase assay. Prospective studies evaluating their sensitivity and specificity are lacking. Objectives To compare the results of the Spec fPL and the DGGR assays with a standardized histologic assessment of the pancreas. Animals Sixty client-owned cats presented for necropsy. Methods Prospective study: Spec fPL concentrations and serum DGGR lipase activity were measured from the same blood sample. The pancreas was removed within 3 hours after euthanasia; serial transverse sections were made every 0.5 cm throughout the entire pancreas and reviewed using a histologic grading scheme. Sensitivity and specificity for the Spec fPL and DGGR assay results were determined. Results The sensitivity and specificity for the Spec fPL assay (cutoff value ≥5.4 μg/L) was 42.1 [95% confidence interval (95% CI), 29.4-55.9%] and 100% (95% CI, 31.0-100.0%). The sensitivity and specificity for the DGGR assay (cutoff value >26 U/L) was 36.8 (95% CI, 24.7-50.7%) and 100% (95% CI, 31.0-100.0%). When lymphocytic inflammation up to 10% of a section was considered normal, the sensitivity and specificity for Spec fPL assay (cutoff value ≥5.4 μg/L) was 61.1 (95% CI, 36.1-81.7%) and 69.0% (95% CI, 52.8-81.9%) and the sensitivity and specificity for the DGGR assay (cutoff value >26 U/L) was 66.7 (95% CI, 41.2-85.6%) and 78.6% (95% CI, 62.8-89.2%). Conclusions and Clinical Importance Both lipase assays performed similarly well, but their agreement with histologic pancreatic inflammation was limited. [ABSTRACT FROM AUTHOR]

Published
2016
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37. Effect of the Glucagon-like Peptide-1 Analogue Exenatide Extended Release in Cats with Newly Diagnosed Diabetes Mellitus.

Author

Riederer, A., Zini, E., Salesov, E., Fracassi, F., Padrutt, I., Macha, K., Stöckle, T.M., Lutz, T.A., and Reusch, C.E.

Subjects
GLUCAGON, PEPTIDES, EXENATIDE, FELINE diabetes, INSULIN
Abstract

Background Exenatide extended release ( ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. Objectives The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. Animals Thirty client-owned cats. Methods Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. Results Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group ( P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% ( P = .427 and P = .178, respectively). Conclusion and clinical importance Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively. [ABSTRACT FROM AUTHOR]

Published
2016
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