ALTERATIONS IN DNA METHYLATION IN COLONIC ADENOCARCINOMA

有人认为，癌症是DNA的一种改变， 可由后代细胞遗传，这导致了异常调节 正常细胞基因的表达。在这里提出的实验中，我们 我想探讨基因甲基化状态的变化 代表了癌症中这种DNA改变的一类。这些实验 是由两组观察结果引起的。第一组包括 大量研究表明，DNA甲基化的变化伴随着 正常基因的调控表达，以及由此导致的DNA减少 甲基化导致低甲基化基因的表达。第二 一组观察包括我们自己对少数人的研究 癌症患者；我们已经发现特定的基因惊人地 一些癌症组织中的低甲基化与它们的 正常的对应物。我们希望通过一个 一种常见的人类结肠癌DNA甲基化的详细研究 腺癌。我们将研究几个基因的甲基化 这些癌症的数量来确定这种形式的DNA的流行率 结肠癌的改变。然后，我们将确定 基因的甲基化状态与这些基因的异常表达有关 癌组织中的基因。最后，我们将确定是否存在 DNA甲基化改变与基础恶性之间的关系 肿瘤进展、转移和异质性等过程。

It has been suggested that cancer represents an alteration in DNA, heritable by progeny cells, that leads to the abnormally regulated expression of normal cellular genes. In the experiments proposed here, we wish to explore the idea that changes in the methylation status of genes represent one class of such DNA alterations in cancer. These experiments were prompted by two sets of observations. The first set comprises the large number of studies showing that changes in DNA methylation accompany the regulated expression of normal genes, and that induced decreases in DNA methylation lead to the expression of the hypomethylated genes. The second set of observations comprises our own studies on a small number of human cancer patients; we have found that specific genes are strikingly hypomethylated in some of the cancerous tissues when compared to their normal counterparts. We wish to extend these observations through a detailed study of DNA methylation in a common form of human cancer, colonic adenocarcinoma. We will study the methylation of several genes in a large number of these cancers to determine the prevalence of this form of DNA alteration in colon cancer. We will then determine whether changes in the methylation status of genes is associated with abnormal expression of these genes in the cancerous tissues. Finally, we will determine whether there is a correlation between alterations in DNA methylation and basic malignant processes such as tumor progression, metastasis, and heterogeneity.