The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
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DOI：
10.1016/s0002-9440(10)63279-8
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发表时间：
2004-07-01
影响因子：
6
通讯作者：
Van de Rijn, M
中科院分区：
文献类型：
--
作者：
West, RB;Corless, CL;Van de Rijn, M
我们最近利用基因芯片研究了胃肠道间质瘤(GIST)中的基因表达模式，发现编码假想蛋白的基因FLJ1 0261(Dog1，在GIST-1上发现)在GIST中特异表达。在两个软组织肿瘤微阵列上评估了兔抗狗1肽的免疫反应性。组织芯片包括587个软组织肿瘤，149个GIST，包括127个已知Kit和PDGFRA突变状态的GIST病例。139例可评分的GIST中有136例(97.8%)有Dog1的Inummore活性。所有7例具有PDGFRA突变的GIST病例均为Dog1阳性，而大多数病例对KIT没有反应。免疫组织化学。Dog1、Kit和PDGFRA的原位杂交探针证实了这一发现。其他在GIST鉴别诊断中的肿瘤，包括硬纤维瘤病(0/17)和神经鞘瘤(0/3)，Dog1免疫阴性。在438例非胃肠道间质瘤中，仅4例为DOG1免疫阳性。DOG1是一种功能未知的蛋白，在胃肠道间质瘤细胞表面表达较强，在其他软组织肿瘤中很少表达。Dog1的反应性可能有助于GIST的诊断，包括未能表达KIT抗原的PDGFRA突变体，并导致使用KIT酪氨酸激酶抑制剂甲磺酸伊马替尼进行适当的治疗。
We recently characterized gene expression patterns in gastrointestinal stromal tumors (GISTs) using cDNA microarrays, and found that the gene FLJ1 0261 (DOG1, discovered on GIST-1), encoding a hypothetical protein, was specifically expressed in GISTs. The immunoreactivity of a rabbit antiscerum to synthetic DOG1 peptides was assessed on two soft tissue tumor microarrays. The tissue microarrays included 587 soft tissue tumors, with 149 GISTs, including 127 GIST cases for which the KIT and PDGFRA mutation status was known. Inummoreactivity for DOG1 was found in 136 of 139 (97.8%) of scorable GISTs. All seven GIST cases with a PDGFRA mutation were DOG1-positive, while most of these failed to react for KIT. The immunohistochemical. findings were confirmed with in situ hybridization probes for DOG1, KIT, and PDGFRA. Other neoplasms in the differential diagnosis of GIST, including desmoid fibromatosis (0 of 17) and Schwannoma (0 of 3), were immunonegative for DOG1. Only 4 of 438 non-GIST cases were immunoreactive for DOG1. DOG1, a protein of unknown function, is expressed strongly on the cell surface of GISTs and is rarely expressed in other soft tissue tumors. Reactivity for DOG1 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase.