Klump B, Hsieh C J, Holzmann K, Gregor M, Porschen R
Department of Medicine I, University Hospital of Tübingen, T ubingen, Germany. bodo.klump@uni-tuebin
Gastroenterology. 1998 Dec;115(6):1381-6. doi: 10.1016/s0016-5085(98)70016-2.
BACKGROUND & AIMS: Inactivation of the CDKN2/p16(INK4A) tumor-suppressor gene is one of the most frequent genetic alterations in human malignancies. In esophageal adenocarcinomas, mutations of the p16 gene or homozygous deletions of the gene locus 9p21 are rare. This study investigated whether p16 promoter hypermethylation is an alternative mechanism for p16 gene inactivation during neoplastic progression in Barrett's esophagus.
A methylation-specific polymerase chain reaction protocol was applied. A total of 95 specimens from 14 patients with Barrett's esophagus were analyzed longitudinally. The p16 promoter status was compared with histomorphological findings.
p16 promoter hypermethylation was detected in 9 of the 10 patients who had displayed dysplasia at some time during surveillance, whereas none of the patients who had not displayed dysplasia during surveillance had p16 promoter hypermethylation. p16 promoter hypermethylation was detected in 3% (2 of 67) of the samples without dysplasia, 60% (3 of 5) of the samples with lesions indefinite for dysplasia, 55.6% (10 of 18) of the specimens with low-grade dysplasia, and 75% (3 of 4) of the specimens with high-grade dysplasia.
These data suggest that p16 promoter hypermethylation is a common mechanism of p16 gene inactivation during neoplastic progression in Barrett's esophagus.
CDKN2/p16(INK4A)肿瘤抑制基因失活是人类恶性肿瘤中最常见的基因改变之一。在食管腺癌中，p16基因的突变或9p21基因位点的纯合缺失很少见。本研究调查了p16启动子高甲基化是否是巴雷特食管肿瘤进展过程中p16基因失活的另一种机制。
应用甲基化特异性聚合酶链反应方案。对14例巴雷特食管患者的95份标本进行纵向分析。将p16启动子状态与组织形态学结果进行比较。
在10例在监测期间出现过发育异常的患者中，有9例检测到p16启动子高甲基化，而在监测期间未出现发育异常的患者中，无一例检测到p16启动子高甲基化。在无发育异常的样本中，3%（67份中的2份）检测到p16启动子高甲基化；在发育异常不明确的病变样本中，60%（5份中的3份）检测到；在低级别发育异常的标本中，55.6%（18份中的10份）检测到；在高级别发育异常的标本中，75%（4份中的3份）检测到。
这些数据表明，p16启动子高甲基化是巴雷特食管肿瘤进展过程中p16基因失活的常见机制。
