Gene promoter hypermethylation in tumors and serum of head and neck cancer patients.
Gene promoter hypermethylation in tumors and serum of head and neck cancer patients.
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发表时间：
2000-02
期刊：
影响因子：
11.2
通讯作者：
M. Sanchez-Cespedes;M. Esteller;Li Wu;H. Nawroz-Danish;G. Yoo;W. Koch;Jin Jen;J. Herman;D. Sidransky
中科院分区：
文献类型：
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作者：
M. Sanchez-Cespedes;M. Esteller;Li Wu;H. Nawroz-Danish;G. Yoo;W. Koch;Jin Jen;J. Herman;D. Sidransky
启动子高甲基化是抑制癌细胞基因转录的重要途径。我们分析了 95 名头颈癌患者原发性肿瘤中四个基因的异常 DNA 甲基化，然后使用这种甲基化的存在作为血清 DNA 中癌细胞检测的标记。通过甲基化特异性 PCR 测试了这四个基因，包括：p16 (CDKN2A)、O6-甲基鸟嘌呤-DNA-甲基转移酶、谷胱甘肽 S-转移酶 P1 和死亡相关蛋白激酶 (DAP-激酶)。 55%（95 人中的 52 人）的原发性肿瘤至少在一个所研究的基因中表现出启动子高甲基化：27%（26/95）在 p16，33%（95 人中的 31 人）在 O6-甲基鸟嘌呤-DNA-甲基转移酶； 18%（92 人中的 17 人）为 DAP 激酶。在谷胱甘肽 S-转移酶 P1 基因启动子处未观察到启动子高甲基化。我们检测到 DAP 激酶基因启动子高甲基化的存在与淋巴结受累 (P = 0.014) 和晚期疾病阶段 (P = 0.016) 之间存在统计学上显着的相关性。在 50 例可用于表观遗传学分析的配对血清中，在 21 例（42%）例的相应血清 DNA 中检测到相同的甲基化模式。在血清DNA甲基化的患者中，有5例发生远处转移，而血清启动子高甲基化阴性的患者仅有1例发生转移（P = 0.056）。关键通路中关键基因的启动子高甲基化在头颈癌中很常见，是监测受影响患者的有前途的血清标志物。
Promoter hypermethylation is an important pathway for repression of gene transcription in cancer cells. We analyzed aberrant DNA methylation at four genes in primary tumors from 95 head and neck cancer patients and then used the presence of this methylation as a marker for cancer cell detection in serum DNA. These four genes were tested by methylation-specific PCR and included: p16 (CDKN2A), O6-methylguanine-DNA-methyltransferase, glutathione S-transferase P1, and death-associated protein kinase (DAP-kinase). Fifty-five % (52 of 95) of the primary tumors displayed promoter hypermethylation in at least one of the genes studied: 27% (26/95) at p16, 33% (31 of 95) at O6-methylguanine-DNA-methyltransferase; and 18% (17 of 92) at DAP-kinase. No promoter hypermethylation was observed at the glutathione S-transferase P1 gene promoter. We detected a statistically significant correlation between the presence of DAP-kinase gene promoter hypermethylation and lymph node involvement (P = 0.014) and advanced disease stage (P = 0.016). In 50 patients with paired serum available for epigenetic analysis, the same methylation pattern was detected in the corresponding serum DNA of 21 (42%) cases. Among the patients with methylated serum DNA, 5 developed distant metastasis compared with the occurrence of metastasis in only 1 patient negative for serum promoter hypermethylation (P = 0.056). Promoter hypermethylation of key genes in critical pathways is common in head and neck cancer and represents a promising serum marker for monitoring affected patients.