Aberrant p16 Methylation, a Possible Epigenetic Risk Factor in Familial Esophageal Squamous Cell Carcinoma
Aberrant p16 Methylation, a Possible Epigenetic Risk Factor in Familial Esophageal Squamous Cell Carcinoma
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DOI：
10.1385/ijgc:36:1:047
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发表时间：
2005-08-01
影响因子：
1.6
通讯作者：
Ghavamnasiry, Mohammad Reza
中科院分区：
文献类型：
--
作者：
Abbaszadegan, Mohammad Reza;Raziee, Hamid Reza;Ghavamnasiry, Mohammad Reza
瞄准p16基因是细胞周期蛋白D依赖性蛋白激酶的抑制剂，检测其甲基化可作为食管鳞状细胞癌（ESCC）早期诊断的新肿瘤标志物。在伊朗东北部呼罗珊省评估了一个具有ESCC聚集性的大家庭。该家族连续两代有三例经组织学证实的ESCC病例，其他几例死者有ESCC病史。应用甲基化特异性PCR（MSP）检测28例ESCC家系连续三代成员、30例散发性ESCC患者（血清、血液和肿瘤组织）和30例健康志愿者（血液）的p16基因启动子甲基化状态。在64.3%（n = 28）的ESCC家族成员中发现异常的p16启动子甲基化，而在我们的正常志愿者中没有发现异常的p16启动子甲基化。在28名有食管癌症状的家庭成员中，有5名ESCC的内镜检查结果为阴性，而其中4名成员的血液中有p16高甲基化。通过定期检查和色素内镜检查，密切监测内镜检查阴性和p16启动子甲基化阳性的家庭成员是否有ESCC发展的迹象。在伊朗东北部的散发性ESCC中，73.3%（n = 30）的肿瘤组织样本具有p16高甲基化。同一患者的血清和血液样本分别有26.6%和43.3%的样本存在p16高甲基化。p16甲基化异常可能是一个有价值的诊断工具，作为一个肿瘤标志物，早期识别个体的高危ESCC家庭。
Aim. Detection of methylation in the p16 gene, an inhibitor of cyclin D-dependent protein kinase, as a new tumor marker for early detection of esophageal squamous cell carcinoma (ESCC) in DNA derived from blood and serum.Method. Alarge family with clustering of ESCC was assessed in Khorasan province in northeastern Iran. The family had three histologically proven cases of ESCC in two consecutive generations and several other deceased cases with histories of ESCC. DNA from blood of 28 living family members in three consecutive generations, 30 sporadic ESCC cases (from serum, blood, and tumor tissues), and 30 healthy volunteers (from blood) were examined for the methylation status of p16 promoter using methylation-specific PCR (MSP).Results. Aberrant p16 promoter methylation was found in 64.3% (n = 28) of ESCC family members and none (n = 30) of our normal volunteers. Five of the 28 family members with esophageal cancer symptoms had negative endoscopy results for ESCC, while four of these members had p16 hypermethylation in their blood. The family members with negative endoscopy and positive p16 promoter methylation are being monitored closely for signs of ESCC development through regular check-ups and chromoendoscopies. In sporadic ESCC in northeastern Iran, 73.3% (n = 30) of tumor tissue samples had p16 hypermethylation. Serum and blood samples from the same patients showed p16 hypermethylation in 26.6% and 43.3% of the samples, respectively.Conclusion. Aberrant p16 methylation may be a valuable diagnostic tool as a tumor marker for the early identification of individuals in high risk ESCC families.