West Robert B, Corless Christopher L, Chen Xin, Rubin Brian P, Subramanian Subbaya, Montgomery Kelli, Zhu Shirley, Ball Catherine A, Nielsen Torsten O, Patel Rajiv, Goldblum John R, Brown Patrick O, Heinrich Michael C, van de Rijn Matt
Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA.
Am J Pathol. 2004 Jul;165(1):107-13. doi: 10.1016/S0002-9440(10)63279-8.
We recently characterized gene expression patterns in gastrointestinal stromal tumors (GISTs) using cDNA microarrays, and found that the gene FLJ10261 (DOG1, discovered on GIST-1), encoding a hypothetical protein, was specifically expressed in GISTs. The immunoreactivity of a rabbit antiserum 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. Immunoreactivity 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.
我们最近利用cDNA微阵列对胃肠道间质瘤（GISTs）中的基因表达模式进行了特征分析，发现编码一种假定蛋白的基因FLJ10261（DOG1，在GIST - 1上发现）在GISTs中特异性表达。在两个软组织肿瘤微阵列上评估了兔抗血清对合成DOG1肽的免疫反应性。该组织微阵列包括587个软组织肿瘤，其中有149个GISTs，包括127个已知KIT和PDGFRA突变状态的GIST病例。在139个可评分的GISTs中有136个（97.8%）发现了DOG1的免疫反应性。所有7例携带PDGFRA突变的GIST病例均为DOG1阳性，而其中大多数对KIT无反应。DOG1、KIT和PDGFRA的原位杂交探针证实了免疫组化结果。GIST鉴别诊断中的其他肿瘤，包括硬纤维瘤（17例中0例）和神经鞘瘤（3例中0例），对DOG1均为免疫阴性。438例非GIST病例中只有4例对DOG1有免疫反应性。DOG1是一种功能未知的蛋白，在GISTs的细胞表面强烈表达，在其他软组织肿瘤中很少表达。DOG1反应性可能有助于GISTs的诊断，包括那些不表达KIT抗原的PDGFRA突变体，并有助于指导使用甲磺酸伊马替尼（一种KIT酪氨酸激酶抑制剂）进行适当治疗。
