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DNA Methylation Markers in Esophageal Adenocarcinoma

食管腺癌中的 DNA 甲基化标志物

基本信息

批准号：
7121051
负责人：
PETER W LAIRD
金额：
$ 35.7万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-26 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7121051
关键词：
Barretts esophagus DNA methylation adenocarcinoma biomarker clinical research disease /disorder proneness /risk early diagnosis esophagus neoplasm human genetic material tag human subject human tissue interview longitudinal human study neoplasm /cancer diagnosis polymerase chain reaction questionnaires

项目摘要

DESCRIPTION (provided by applicant): In recent years, it has become clear that molecular events leading to oncogenesis include not only genetic mutations, but also epigenetic alterations, such as the DNA methylation of promoter CpG islands. We have shown that DNA methylation changes are both causal contributors to neoplasia, and potential biomarkers for cancer, including adenocarcinoma of the esophagus. We have developed a sensitive, quantitatively accurate, automated DNA methylation analysis technique, called MethyLight, with which we have shown that DNA methylation profiles can discriminate between normal squamous mucosa of the esophagus, intestinal metaplasia, and dysplasia. These preliminary results suggest that DNA methylation markers could eventually be exploited as clinical tools in the early detection of esophageal adenocarcinoma and/or in risk assessment in surveillance programs. Since the 1970s, incidence rates for esophageal and gastric cardia adenocarcinomas have risen substantially, particularly among white males in the United States. Reasons for the increase of these tumor types are not well understood. We have conducted a case-control study to determine the role of smoking, alcohol use, body size characteristics, and other risk factors in the etiology of adenocarcinoma of the esophagus and gastric cardia. Here we propose to use automated MethyLight technology to generate extensive methylation profiles for tissue samples retrieved from this population-based case-control study. This will allow us to identify superior methylation markers for further development and testing as clinical tools in the early detection of esophageal adenocarcinoma, and for the differentiation of Barrett's cases that are at high risk for further progression. We will also investigate whether factors known to increase the risk of adenocarcinoma of the esophagus, increase the risk of DNA methylation in normal tissue, or in the resulting adenocarcinoma.

描述（由申请人提供）：近年来，已经清楚的是，导致肿瘤发生的分子事件不仅包括基因突变，还包括表观遗传改变，例如启动子CpG岛的DNA甲基化。我们已经表明，DNA甲基化变化既是肿瘤形成的原因，也是癌症（包括食管腺癌）的潜在生物标志物。我们开发了一种灵敏、定量准确、自动化的DNA甲基化分析技术，称为MethyLight，我们已经证明DNA甲基化谱可以区分食管正常鳞状粘膜、肠化生和异型增生。这些初步结果表明，DNA甲基化标志物最终可以作为临床工具，在食管腺癌的早期检测和/或在监测项目的风险评估。自20世纪70年代以来，食管和贲门腺癌的发病率大幅上升，特别是在美国的白色男性中。这些肿瘤类型增加的原因尚不清楚。我们进行了一项病例对照研究，以确定吸烟、饮酒、体型特征和其他危险因素在食管和贲门腺癌病因学中的作用。在这里，我们建议使用自动化的MethyLight技术，以产生广泛的甲基化配置文件的组织样本从这个基于人群的病例对照研究。这将使我们能够确定上级甲基化标志物，以进一步开发和测试作为早期检测食管腺癌的临床工具，并用于区分处于进一步进展的高风险的巴雷特病例。我们还将研究已知的因素是否增加食管腺癌的风险，增加正常组织或腺癌中DNA甲基化的风险。