EXPOSURE SPECIFIC MUTATION IN CRITICAL TARGET GENES

工作总结：肺癌和膀胱癌 与环境暴露有很强的联系，使它们 合适的肿瘤在其中检验不同的假设 环境暴露会导致不同模式的基因突变 启动致癌的基因。我们设计了一系列 对这一假设进行检验的研究。对于肺癌，这包括研究 科罗拉多州和捷克斯洛伐克的铀矿工；镍冶炼厂 接触石棉的工人和接触氯乙烯的工人 挪威的工人，以及来自美国的吸烟者和不吸烟者。 对于膀胱癌，它包括对接触芳香胺的工人的研究 佐治亚州和新泽西州的杜邦员工， 来自丹麦的接受环磷酰胺治疗的患者和吸烟者 和来自美国的非吸烟者。我们已经出版了一系列 关于ras、p53、p15和p16突变和杂合性缺失的文献 这些研究。过去一年的努力主要集中在 发展新的临床协作和实验室 比较基因组杂交技术(CGH)的发展 固定的组织。与加州大学肺内科诊所 北卡罗来纳州我们正在开展对分子事件的研究 应用荧光支气管镜检查早期癌前病变。 荧光支气管镜检查可检测不典型的病变 使用常规的光支气管镜检查可见，这种损害可以 做了活组织检查，并随着时间的推移进行了跟踪。此外，我们正在开发一种 与梅奥诊所合作提供肺癌样本 来自有趣的亚组：不吸烟者和第一次吸烟的患者 肺癌的学位亲属以及以人群为基础的 样本。在实验室方面，帕克纳姆博士一直在研究 用精选的固定膀胱癌样本发展为退行性变 寡核苷酸启动(DOP)聚合酶链式反应允许我们在 固定的组织标本。

Summary of Work: Lung and bladder cancers have strong associations with environmental exposures, making them appropriate tumors in which to test the hypothesis that different environmental exposures cause different patterns of mutations in gene that initiate carcinogenesis. We have designed a series of studies to test this hypothesis. For lung cancer this includes studies of uranium miners in Colorado and Czechoslovakia; nickel smelter workers, asbestos-exposed workers, and vinyl chloride- exposed workers in Norway; and smokers and non-smokers from the U.S. For bladder cancer it includes studies of arylamine-exposed workers in Georgia and of DuPont workers in New Jersey, cyclophosphamide-treated patients from Denmark, and smokers and non-smokers from the U.S. We have published a series of papers on ras, p53, and p15 and p16 mutations and LOH from these studies. Efforts in the past year have been directed at developing new clinical collaborations and the laboratory development of comparative genomic hybridization (CGH) from fixed tissue. With the Pulmonary Medicine Clinic at University of North Carolina we are developing a study of the molecular events in early preneoplastic lesions utilizing fluorescent bronchoscopy. Fluorescent bronchoscopy allows detection of dysplastic lesions not visible using regular light bronchoscopy, and such lesions can be biopsied and followed over time. In addition we are developing a collaboration with the Mayo Clinic to provide lung tumor samples from interesting subgroups: non-smokers, and patients with first degree relatives with lung cancers as well as population-based samples. On the laboratory side, Dr. Packenham has been working with selected fixed bladder cancer samples to develop degenerative oligonucleotide priming (DOP) PCR to allow us to do CGH on fixed tissue specimens.