Korpershoek Esther, Dieduksman Daphne A E R, Grinwis Guy C M, Day Michael J, Reusch Claudia E, Hilbe Monika, Fracassi Federico, Krol Niels M G, Uitterlinden André G, de Klein Annelies, Eussen Bert, Stoop Hans, de Krijger Ronald R, Galac Sara, Dinjens Winand N M
Department of Pathology, Erasmus MC Cancer Institute, University Medical Center, 3015 GD Rotterdam, The Netherlands.
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.
Cancers (Basel). 2019 Apr 30;11(5):607. doi: 10.3390/cancers11050607.
8658860258318000Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D ( and ) 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 and 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; p.Arg38Gln ( = 1) and p.Lys122Arg ( = 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.
8658860258318000最近，在患有自发性嗜铬细胞瘤（PCC）和副神经节瘤（PGL；统称为PPGL）的宠物狗中，发现了编码琥珀酸脱氢酶亚基B和D（ 和 ）的基因发生了基因改变，这表明狗可能是研究人类PPGL的一个有趣的比较模型。为了研究犬类PPGL是否与人类PPGL相似，我们通过免疫组织化学研究了一系列50个犬类PPGL，以确定突触素（SYP）、酪氨酸羟化酶（TH）和琥珀酸脱氢酶亚基A（SDHA）和B（SDHB）的表达。同时，通过桑格测序对25个犬类PPGL进行了 和 基因突变筛查。为了检测大的染色体改变，对11个PPGL进行了单核苷酸多态性（SNP）阵列分析，包括有新鲜冷冻组织的病例。大多数犬类PPGL的免疫组织化学标记呈阳性。对犬类肿瘤的基因筛查在4例中发现了先前描述的变异； p.Arg38Gln（ = 1）和 p.Lys122Arg（ = 3）。此外，SNP阵列显示了大的染色体改变，其中5号染色体的缺失最为常见（在6例有染色体改变的病例中占100%），5号染色体部分与人1号染色体和11号染色体同源。总之，犬类和人类PPGL显示出相似的基因组改变，提示存在共同的种间PPGL相关途径。
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