Gene Expression and DNA Methylation in Barrett's Oesophagus and Oesophageal Adenocarcinoma

食道（食道）是食物和饮料从口腔进入胃的管道。在巴雷特食管中，由于严重的胃食管反流，下食道的正常内膜被一种称为肠化生的异常内膜所取代。胃食管反流是所有疾病中最常见的一种，影响到四分之一的成年人，而巴雷特食管本身发生在0.5 - 1%的成年人中。在少数患有巴雷特食管的患者中，下食道衬里的细胞进一步出现异常，导致发育不良和腺癌（腺细胞型癌）。该项目将提供两种最重要的遗传机制（基因表达和DNA甲基化）的第一个综合图谱，其中Barrett食管演变为Barrett不典型增生和腺癌。本项目研究的标本与以往研究的不同之处在于，它们是在不同时间取自同一患者，因为这些患者的Barrett食管要么保持稳定，要么病情恶化。基本上，所有已知的人类基因都将被研究，被确定为重要的基因的相关性将使用高度精确的方法得到证实。有了这些信息，就有可能开发出基因测试，从而预测哪些患者有可能患上更严重的疾病，包括癌症。在该项目的其他部分，将确定影响食管腺癌患者生存可能性的基因，可能开发一种更准确地识别癌症扩散到淋巴结的患者的简单测试，并将测试一种检测食管腺癌的血液测试。

The oesophagus (gullet) is the tube through which food and drinks pass from the mouth to the stomach. In Barrett's oesophagus, the normal lining of the lower oesophagus is replaced by an abnormal type of lining called intestinal metaplasia as a result of severe gastroesophageal reflux. Gastroesophageal reflux is one of the most common of all diseases, affecting up to a quarter of all adults, and Barrett's oesophagus itself occurs in 0.5 - 1% of the adult population. In a minority of patients with Barrett's oesophagus, further abnormalities in the cells lining the lower oesophagus occur, leading to dysplasia and adenocarcinoma (glandular cell type cancer). This project will provide the first comprehensive map of two of the most important genetic mechanisms (gene expression and DNA methylation) by which Barrett's oesophagus evolves into Barrett's dysplasia and adenocarcinoma. The specimens studied in this project differ from previous studies in that they are taken from the same patients at different times, as these patients' Barrett's oesophagus either remains stable or progresses to worse disease. Essentially all the known human genes will be studied and the relevance of genes identified as important will be confirmed using highly accurate methods. With this information, it may be possible to develop genetic tests that can predict which patients are at risk of developing worse disease including cancer. In other parts of this project, genes which influence the likelihood of survival for patients with oesophageal adenocarcinoma will be identified, a simple test to more accurately identify patients with cancer spread to lymph nodes may be developed, and a blood test to detect oesophageal adenocarcinoma will be tested.