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实体瘤中 STAG2 基因的突变和表达分析。

Mutational and expressional analyses of STAG2 gene in solid cancers.

机构信息

Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Neoplasma. 2012;59(5):524-9. doi: 10.4149/neo_2012_067.

Abstract

Aneuploidy is frequently observed in cancers and is considered a crucial mechanism in cancer development. STAG2 is a gene that encodes a component of cohesion complex required for normal chromosomal segregation. Recently, somatic mutation of STAG2 gene and loss of STAG2 protein have been reported in glioblastoma, Ewing's sarcoma and melanoma. The aim of this study was to see whether such alterations of STAG2 are also common in other cancers. In this study, we analyzed STAG2 somatic mutation in 45 colorectal carcinomas (CRC), 45 gastric carcinomas (GC), 45 breast carcinomas, 45 non-small cell lung cancers and 45 prostate carcinomas (PCA) by single-strand conformation polymorphism. We analyzed also STAG2 protein expression in 100 GC, 103 CRC and 107 PCA by immunohistochemistry. STAG2 protein was well expressed in normal stomach, colon and prostate epithelial cells, while it was lost in 27% of GC, 23% of CRC and 30% of PCA. The loss of STAG2 was observed irrespective of subtypes, stages and grades of the cancers. However, we could not find any STAG2 mutations in these cancers. The loss of expression of STAG2 in GC, CRC and PCA tissues compared to their corresponding normal cells indicates that STAG2 loss is common in carcinomas as well. The data suggest also that loss of expression of STAG2, but not somatic mutation, might be responsible to STAG2 inactivation and is common in studied types of carcinomas.

摘要

非整倍体经常在癌症中观察到,被认为是癌症发展的关键机制。STAG2 是一种基因,它编码正常染色体分离所必需的凝聚复合物的一个组成部分。最近,在胶质母细胞瘤、尤因肉瘤和黑色素瘤中已经报道了 STAG2 基因的体细胞突变和 STAG2 蛋白的缺失。本研究的目的是观察 STAG2 的这种改变是否也常见于其他癌症。在这项研究中,我们通过单链构象多态性分析了 45 例结直肠癌(CRC)、45 例胃癌(GC)、45 例乳腺癌、45 例非小细胞肺癌和 45 例前列腺癌(PCA)中的 STAG2 体细胞突变。我们还通过免疫组织化学分析了 100 例 GC、103 例 CRC 和 107 例 PCA 中的 STAG2 蛋白表达。STAG2 蛋白在正常胃、结肠和前列腺上皮细胞中表达良好,而在 27%的 GC、23%的 CRC 和 30%的 PCA 中丢失。STAG2 的丢失与癌症的亚型、分期和分级无关。然而,我们在这些癌症中没有发现任何 STAG2 突变。与相应的正常细胞相比,GC、CRC 和 PCA 组织中 STAG2 的表达缺失表明 STAG2 缺失也常见于癌组织。该数据还表明,STAG2 表达缺失而不是体细胞突变可能导致 STAG2 失活,并且在研究的几种类型的癌中很常见。

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