METHYLATION OF THE CALCITONIN GENE IN HUMAN TUMORS

人类肿瘤中降钙素基因的甲基化

• 批准号: 3185507
• 负责人: STEPHEN B. BAYLIN
• 金额: $ 15.01万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3185507
• 关键词: DNA methylation; adrenocorticotropic hormone; azacitidine; calcitonin; cell differentiation; gel electrophoresis; gene expression; genes; genetic transcription; human tissue; insulin; lung neoplasms; lymphoma; messenger RNA; methylation; molecular genetics; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; nucleic acid hybridization; oogenesis; respiratory epithelium; small cell lung cancer; somatostatin; tissue /cell culture

The current proposal represents our continued studies of the histogenesis and differentiation lineages underlying the formation of the major forms of human lung cancer. We will focus upon initial findings that the 5' region of the calcitonin gene has a unique hypermethylation pattern in DNA extracted from patients with lung cancer and with lymphomas. Among the spectrum of lung cancers, the hypermethylation pattern is most extensive in classic small cell lung cancer (SCLC) and a less extensive, but abnormal pattern, is also found more frequently in so-called "variant" SCLC cells. Within the spectrum of the major types of human lung cancer, the incidence for the presence of the abnormal methylation pattern parallels that for the distribution of a marker for neuroendocrine differentiation. The present studies are designed to extend our observations regarding the incidence of the abnormal methylation pattern in human cancers, to determine whether the patterns are unique to tumor DNA or might reflect the cell compartments in normally renewing adult tissues from which individual types of lung cancers and/or lymphomas arise, to correlate the degree of hypermethylation with patterns of expression for the CT gene, and to ascertain whether the methylation patterns might serve as markers for refining the diagnostic categories of lung cancer in a clinically significant manner. Techniques to be used in these studies include cell culture, DNA-DNA hybridization, DNA-RNA hybridization, Southern and Northern blotting techniques.

当前的提议代表了我们对 组织发生和分化谱系 人类肺癌的主要形式的形成。 我们将 着重于初始发现， 降钙素基因在DNA中具有独特的高甲基化模式 从肺癌和淋巴瘤患者中提取。 在肺癌的光谱中，高甲基化 在经典的小细胞肺癌中，图案最为广泛 （SCLC），并且较少但异常的模式也是 在所谓的“变体” SCLC细胞中发现了更频繁的发现。 在主要类型的人类肺癌的范围内 存在异常甲基化的发生率 图案与分布的标记相似 神经内分泌分化。 目前的研究是 旨在扩展我们关于发生率的观察 人类癌中的异常甲基化模式，以确定 这些图案是肿瘤DNA独有的还是可能反射的 正常更新成人组织的细胞室 出现哪些单独类型的肺癌和/或淋巴瘤， 将高甲基化程度与模式相关 CT基因的表达，并确定是否确定 甲基化模式可能是完善的标志物 临床上的肺癌诊断类别 重要的方式。 这些研究中要使用的技术 包括细胞培养，DNA-DNA杂交，DNA-RNA 杂交，南部和北印迹技术。