p14（ARF）的高甲基化可能预示着溃疡性结肠炎患者患结肠癌的风险。

Hypermethylation of p14 (ARF) may be predictive of colitic cancer in patients with ulcerative colitis.

作者信息

Moriyama Tomohiko, Matsumoto Takayuki, Nakamura Shotaro, Jo Yukihiko, Mibu Ryuichi, Yao Takashi, Iida Mitsuo

机构信息

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka, Japan.

出版信息

Dis Colon Rectum. 2007 Sep;50(9):1384-92. doi: 10.1007/10350-007-0302-x.

DOI:10.1007/10350-007-0302-x

PMID:17665255

Abstract

PURPOSE

The microsatellite instability and CpG island hypermethylation of p14 ( ARF ) and p16 ( INK4a ) are related to the pathogenesis of neoplasia in ulcerative colitis. This study was designed to assess the significance of those genetic or epigenetic alterations for cancer surveillance in ulcerative colitis.

METHODS

During surveillance colonoscopy in 39 patients with ulcerative colitis, biopsy specimens were obtained from the cecum and the rectum as well as from any other areas suspected of being neoplasia by chromoscopy. Using DNA extracts, the methylation status of p14 ( ARF ) and p16 ( INK4a ) and the microsatellite status were determined.

RESULTS

Microsatellite instability was positive in one of five dysplasias, but it was negative in the cecum and the rectum. The incidence of hypermethylation of p14 ( ARF ) was 0 percent in the cecum, 26 percent in the rectum, and 100 percent in dysplasia, whereas that of p16 ( INK4a ) was 10, 10, and 0 percent, respectively. Patients who were positive for the hypermethylation of p14 ( ARF )in the rectum had a longer duration of ulcerative colitis than those who were negative for such hypermethylation. Two of 10 patients who were positive for p14 ( ARF ) hypermethylation in the rectum and 1 of 29 patients who were negative for the hypermethylation had dysplasia. During the subsequent surveillance of 36 patients, dysplasia was detected in 2 of 8 patients with p14 ( ARF ) hypermethylation and in none of 28 patients without hypermethylation (P = 0.044).

CONCLUSIONS

In patients with ulcerative colitis, hypermethylation of p14 ( ARF ) seems to be associated with an early stage of dysplasia. The hypermethylation may be one of candidates for potential biomarker to identify patients at a high risk of dysplasia.

摘要

目的

p14（ARF）和p16（INK4a）的微卫星不稳定性及CpG岛高甲基化与溃疡性结肠炎肿瘤发生机制相关。本研究旨在评估这些基因或表观遗传学改变在溃疡性结肠炎癌症监测中的意义。

方法

在对39例溃疡性结肠炎患者进行监测结肠镜检查期间，从盲肠、直肠以及经染色内镜检查怀疑有肿瘤形成的其他任何部位获取活检标本。使用DNA提取物，确定p14（ARF）和p16（INK4a）的甲基化状态以及微卫星状态。

结果

5例发育异常中有1例微卫星不稳定性呈阳性，但盲肠和直肠中均为阴性。p14（ARF）高甲基化的发生率在盲肠中为0%，直肠中为26%，发育异常中为100%，而p16（INK4a）的高甲基化发生率分别为10%、10%和0%。直肠中p14（ARF）高甲基化呈阳性的患者，其溃疡性结肠炎病程比该高甲基化呈阴性的患者更长。直肠中p14（ARF）高甲基化呈阳性的10例患者中有2例发生发育异常，该高甲基化呈阴性的29例患者中有1例发生发育异常。在随后对36例患者的监测中，8例p14（ARF）高甲基化患者中有2例检测到发育异常，28例无高甲基化患者中均未检测到发育异常（P = 0.044）。