Sato Fumiaki, Shibata David, Harpaz Noam, Xu Yan, Yin Jing, Mori Yuriko, Wang Suna, Olaru Andreea, Deacu Elena, Selaru Florin M, Kimos Martha C, Hytiroglou Prodromos, Young Joanne, Leggett Barbara, Gazdar Adi F, Toyooka Shinichi, Abraham John M, Meltzer Stephen J
Gastroenterology Division, Department of Medicine, University of Maryland School of Medicine and Gastroenterology Service, Baltimore, Maryland 21201, USA.
Cancer Res. 2002 Dec 1;62(23):6820-2.
The HPP1 gene was cloned as a frequently methylated gene in hyperplastic polyps of the colon. It has been shown that HPP1 expression is silenced by HPP1 gene hypermethylation in sporadic colorectal cancers. To determine the role of HPP1 in ulcerative colitis (UC)-associated carcinogenesis, the prevalence of HPP1 methylation was investigated in three different histological stages of UC-associated carcinogenesis (non-neoplastic UC colon, dysplasia, and carcinoma). Quantitative methylation-specific PCR and quantitative reverse transcription-PCR were used to determine HPP1 gene methylation and expression levels, respectively. HPP1 methylation was observed in 24 of 48 (50%) adenocarcinomas and in 4 of 10 (40%) dysplasias. In contrast, no non-neoplastic UC mucosa showed HPP1 methylation. HPP1 expression in the HCT116 colon cancer cell line was restored after treatment with the demethylating agent 5-aza-2'-deoxycytidine. In conclusion, our data suggest that methylation of HPP1 is a relatively common early event in UC-associated carcinogenesis. HPP1 offers potential as a biomarker for the early detection of cancer or dysplasia in UC.
HPP1基因作为结肠增生性息肉中频繁甲基化的基因被克隆出来。研究表明，在散发性结直肠癌中，HPP1基因的高甲基化会使HPP1表达沉默。为了确定HPP1在溃疡性结肠炎（UC）相关癌变中的作用，我们研究了UC相关癌变的三个不同组织学阶段（非肿瘤性UC结肠、发育异常和癌）中HPP1甲基化的发生率。分别使用定量甲基化特异性PCR和定量逆转录PCR来测定HPP1基因的甲基化和表达水平。在48例腺癌中有24例（50%）以及10例发育异常中有4例（40%）观察到HPP1甲基化。相比之下，非肿瘤性UC黏膜未显示HPP1甲基化。用去甲基化剂5-氮杂-2'-脱氧胞苷处理后，HCT116结肠癌细胞系中的HPP1表达得以恢复。总之，我们的数据表明，HPP1甲基化是UC相关癌变中相对常见的早期事件。HPP1有潜力作为UC中癌症或发育异常早期检测的生物标志物。
