Development of DNA Methylation Markers for Early Detection of Lung Cancer

在美国，肺癌是所有种族男性和女性癌症死亡的主要原因 组。这种主要由吸烟引起的疾病，2005年将导致超过16万美国人死亡。在……里面 2002/2003年，据估计，20-25%的男性和女性以及近22%的高中生吸烟。 肺癌患者的存活率很低，很大程度上是因为这种疾病很难在早期被发现 阶段，那时它仍然可以通过手术治愈。先进的成像技术，如螺旋计算机 断层扫描可以对肺部进行高分辨率检查，但不会进展为肺癌的病变是 在长期重度吸烟者中非常常见。可以在人体内检测到的分子标记 早期肺癌患者的体液将是一种非常强大的补充成像手段。 技术，这将允许从可疑的肺癌患者中识别出真正的肺癌患者 损伤。DNA超甲基化是DNA的一种修饰，它不会改变它的序列，但它会改变 基因表达的能力。在癌症中经常观察到异常增加的甲基化， 它会导致正常情况下控制细胞生长和细胞存活的基因沉默。到目前为止，一个 已经确定了一些显示甲基化增加的基因，但这些基因中的许多没有 在肺癌中，甲基化的比例足够高，可以作为标志物。使用高吞吐量 南加州大学开发的系统，莱尔德-奥林加实验室最近发现了一些非常强大的 肺癌中甲基化的候选标记物。这项提案旨在验证这些 300例档案肺标本和300例配对标本对所有主要类型非小细胞肺癌标志物的研究 控制(来自同一患者的)非肿瘤性肺癌以及100例转移到 阿龙。所有主要种族(白人、黑人、西班牙裔/拉丁裔和亚洲/太平洋岛民)的肺标本 将会被检查。这些标记物通过对患者身体的分析来检测肺癌的能力 将使用一种新的定量技术来确定液体，以检查血浆、痰和/或 在大学医院、莫里斯癌症中心治疗的300名肺癌患者的细支气管肺泡灌洗 洛杉矶县医院。肺癌敏感、特异分子标志物的研究进展 是早期发现本病的关键，并可大大提高肺癌患者的生存率。

In the United States, lung cancer is the leading cause of cancer death in men and women of all ethnic groups. This disease, which is mainly caused by smoking, will kill over 160,000 Americans in 2005. In 2002/2003 it was estimated that 20-25% of men and women and almost 22% of high school students smoke. Survival of lung cancer patients is very poor, largely because the disease is difficult to detect at an early stage, when it could still be cured by surgery. Advanced imaging techniques such as spiral computed tomography allow high resolution examination of the lung, but lesions that do not progress to lung cancer are very frequently observed in longtime heavy smokers. Molecular markers that could be detected in the bodily fluids of early stage lung cancer patients would be a very powerful and complementary addition to imaging techniques, that would allow the identification of true lung cancer patients from among those with suspicious lesions. DNA hypermethylation is a modification of DNA that does not change its sequence, but that alters the ability of genes to be expressed. Abnormally increased methylation is frequently observed in cancer, where it causes the silencing of genes that normally keep cell growth and cell survival in check. To date, a number of genes showing increased methylation have been identified, but many of these genes are not methylated in a high enough percentage of lung cancers to be useful as markers. Using a high-throughput system developed at USC, the Laird-Offringa laboratory has recently identified a number of very strong candidate markers that are hypermethylated in lung cancer. This proposal is aimed at validating these markers in all major types of non-small cell lung cancer using 300 archival lung specimens and 300 matched control non-tumor lung (from the same patients), as well as 100 non-lung cancers that metastasized to the lung. Lung specimens from all major ethnic groups (white, black, Hispanic/Latino and Asian/Pacific Islander) will be examined. The ability of these markers to detect lung cancer through the analysis of patient bodily fluids will be determined using a new quantitative technique to examine the plasma, sputum and/or bronchioalveloar wash of 300 lung cancer patients treated at University Hospital, Morris Cancer Center, and Los Angeles County Hospital. The development of sensitive and specific molecular markers for lung cancer is the key to early detection of this disease, and could greatly increase lung cancer patient survival.