Abou Asa S, Mori T, Maruo K, Khater A, El-Sawak A, Abd el-Aziz E, Yanai T, Sakai H
Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Gifu University, Gifu, Japan.
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Kafr El-Sheikh, Egypt.
Vet Comp Oncol. 2015 Sep;13(3):237-45. doi: 10.1111/vco.12035. Epub 2013 Apr 24.
We examined whether mutation of the platelet-derived growth factor receptor protein tyrosine kinase (PDGFR)-α and PDGFR-β genes contributes to their overexpression in canine vascular tumours. Genomic sequences of trans- or juxtamembrane regions of PDGFR-α and PDGFR-β were analysed with immunohistochemical staining and polymerase chain reaction-direct sequencing using DNA from paraffin-embedded neoplastic tissues of 27 hemangiosarcomas (HSAs) and 20 hemangiomas (HAs). Immunohistochemically, 75% of the HA cases were positive for PDGFR-α and almost most of the HA cases were negative for PDGFR-β. Of the HSA cases, 55.6% were negative for PDGFR-α and 63% were strongly positive for PDGFR-β. Among the HA cases, 1 missense mutation was detected in PDGFR-α exon 18 and 1 in PDGFR-β exon 17. Two HSA cases had missense mutations in exon 14 and 1 in exon 17 of PDGFR-β. Thus, genomic mutation of trans- or juxtamembrane regions of PDGFRs was not the main mechanism driving the activation of receptors in HSA and HA.
我们研究了血小板衍生生长因子受体蛋白酪氨酸激酶（PDGFR）-α和PDGFR-β基因的突变是否导致它们在犬血管肿瘤中过度表达。使用来自27例血管肉瘤（HSAs）和20例血管瘤（HAs）石蜡包埋肿瘤组织的DNA，通过免疫组织化学染色和聚合酶链反应直接测序分析了PDGFR-α和PDGFR-β跨膜或近膜区域的基因组序列。免疫组织化学结果显示，75%的HA病例PDGFR-α呈阳性，几乎所有HA病例PDGFR-β呈阴性。在HSA病例中，55.6%的病例PDGFR-α呈阴性，63%的病例PDGFR-β呈强阳性。在HA病例中，在PDGFR-α外显子18中检测到1个错义突变，在PDGFR-β外显子17中检测到1个错义突变。2例HSA病例在PDGFR-β外显子14中有错义突变，1例在PDGFR-β外显子17中有错义突变。因此，PDGFRs跨膜或近膜区域的基因组突变不是驱动HSA和HA中受体激活的主要机制。
