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Barrett‘s食道中，由于严重的胃食道反流，下段食道的正常衬里被一种称为肠化生的异常衬里所取代。胃食道反流是所有疾病中最常见的疾病之一，影响多达四分之一的成年人，而巴雷特食道本身也发生在0.5%-1%的成年人中。在少数Barrett‘s食道患者中，食道下段的细胞进一步异常，导致不典型增生和腺癌(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)的第一张全面图谱，通过这两种机制，Barrett‘s食道演变为Barrett’s异型增生和腺癌。这个项目中研究的标本与以前的研究不同之处在于，它们是在不同的时间从同一患者身上采集的，因为这些患者的巴雷特食道要么保持稳定，要么病情恶化。基本上，所有已知的人类基因都将被研究，并将使用高度准确的方法确认被确定为重要基因的相关性。有了这些信息，就有可能开发出可以预测哪些患者有患上包括癌症在内的更严重疾病的风险的基因测试。在这个项目的其他部分，将识别影响食管腺癌患者生存可能性的基因，可能会开发一种简单的测试来更准确地识别癌症扩散到淋巴结的患者，并将测试血液测试以检测食管腺癌。

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.