Abbaszadegan Mohammad Reza, Raziee Hamid Reza, Ghafarzadegan Kamran, Shakeri Mohammad Taghi, Afsharnezhad Sima, Ghavamnasiry Mohammad Reza
Division of Human Genetics, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran.
Int J Gastrointest Cancer. 2005;36(1):47-54. doi: 10.1385/IJGC:36:1:047.
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.
A large 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).
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.
Aberrant p16 methylation may be a valuable diagnostic tool as a tumor marker for the early identification of individuals in high risk ESCC families.
检测细胞周期蛋白D依赖性蛋白激酶抑制剂p16基因的甲基化，作为一种新的肿瘤标志物，用于从血液和血清来源的DNA中早期检测食管鳞状细胞癌（ESCC）。
对伊朗东北部霍拉桑省一个ESCC聚集的大家族进行评估。该家族连续两代有3例经组织学证实的ESCC病例，还有其他几例有ESCC病史的死亡病例。采用甲基化特异性PCR（MSP）检测连续三代中28名在世家族成员血液中的DNA、30例散发ESCC病例（血清、血液和肿瘤组织）以及30名健康志愿者（血液）中p16启动子的甲基化状态。
在64.3%（n = 28）的ESCC家族成员中发现p16启动子异常甲基化，而正常志愿者中无一例（n = 30）出现异常甲基化。28名有食管癌症状的家族成员中，5例内镜检查结果为ESCC阴性，其中4例血液中p16甲基化程度较高。对内镜检查阴性且p16启动子甲基化阳性的家族成员通过定期检查和色素内镜检查密切监测ESCC发展迹象。在伊朗东北部的散发ESCC病例中，73.3%（n = 30）的肿瘤组织样本存在p16甲基化程度较高的情况。同一患者的血清和血液样本中，分别有26.6%和43.3%的样本显示p16甲基化程度较高。
异常的p16甲基化可能是一种有价值的诊断工具，作为肿瘤标志物用于早期识别ESCC高危家族中的个体。
