Methylation of death-associated protein kinase in ovarian carcinomas
Methylation of death-associated protein kinase in ovarian carcinomas
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DOI：
10.1111/j.1525-1438.2006.00506.x
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发表时间：
2006-01-01
影响因子：
4.8
通讯作者：
Odunsi, K
中科院分区：
文献类型：
--
作者：
Collins, Y;Dicioccio, R;Odunsi, K
死亡相关蛋白（DAP）激酶是一种丝氨酸/苏氨酸激酶，在细胞凋亡和转移中起着不可或缺的作用。本研究的目的是检测卵巢癌组织中DAP激酶的甲基化状态。研究了1987年至1999年间在纽约布法罗罗斯韦尔公园癌症研究所治疗的31例经组织学证实的上皮性卵巢癌患者。检查62个样品的DAP激酶甲基化状态：1个来自健康个体的正常人基因组DNA样品，1个转化的正常表面卵巢上皮细胞系GOSE，来自Nancy Auersperg博士，温哥华，加拿大），2个卵巢癌细胞系（OVCAR 3和A2780），1个卵巢浆液性囊腺瘤和30个卵巢癌。同时检测浆液性囊腺瘤和卵巢癌患者外周血DNA。使用针对未甲基化和甲基化启动子区设计的引物进行甲基化特异性聚合酶链反应。DAP激酶基因在正常人基因组DNA样品和转化的正常表面上皮卵巢细胞系中均未甲基化。两种卵巢癌细胞系均发生甲基化。在30例恶性肿瘤患者中，20例（67%）观察到DAP激酶甲基化。30例患者中有26例（87%）可获得外周血DNA。配对样本的比较表明，14个（54%）甲基化和12个（46%）未甲基化。DAP激酶甲基化状态与分期、分级、组织学或生存率之间无相关性。DAP激酶基因启动子区CpG岛甲基化在卵巢癌患者外周血DNA和组织样本中很常见。这种分子畸变可能是治疗干预的潜在靶点。
Death-associated protein (DAP) kinase is a serine/threonine kinase that plays an integral role in apoptosis and metastasis. The purpose of our study was to determine the methylation status of DAP kinase in ovarian carcinomas. Thirty-one patients with histologically confirmed epithelial ovarian cancers treated at Roswell Park Cancer Institute, Buffalo, New York, between 1987 and 1999 were studied. Sixty-two samples were examined for DAP kinase methylation status: 1 normal human genomic DNA sample from a healthy individual, 1 transformed normal surface ovarian epithelial cell line GOSE, from Dr Nancy Auersperg, Vancouver, Canada), 2 ovarian carcinoma cell lines (OVCAR3 and A2780), 1 ovarian serous cystadenoma, and 30 ovarian carcinomas. Additionally, peripheral blood DNA was examined from the patients with the serous cystadenoma and ovarian carcinomas. Methylation-specific polymerase chain reaction was performed using primers designed for the unmethylated and methylated promoter regions. The DAP kinase gene was unmethylated in both the normal human genomic DNA sample and the transformed normal surface epithelial ovarian cell line. The two ovarian cancer cell lines were methylated. In the 30 patients with malignant disease, methylation of DAP kinase was observed in 20 (67%). Peripheral blood DNA was available in 26 (87%) of the 30 patients. Comparison of the paired samples indicated that 14 (54%) were methylated and 12 (46%) were unmethylated. There was no correlation between the DAP kinase methylation status and stage, grade, histology, or survival. Methylation of CpG islands in the promoter region of the DAP kinase gene is common in peripheral blood DNA and tissue samples of patients with ovarian carcinomas. This molecular aberration may represent a potential target for therapeutic intervention.