Prognostic Significance of Altered DNA Methylation

描述：(申请人提供)承认吸烟 是肺癌、喉癌和肺癌的常见危险因素 口腔。尽管这些“癌前病变”被确定为 与吸烟有关的癌症，并不是所有的病变都变得恶性，目前存在 没有足够的证据来确定哪些特征可以可靠地预测 此类病变的恶性潜能。我们假设传统的 癌前病变的组织病理学检查提供的不足 关于预后的信息，但这些患者的遗传和表观遗传学改变 病变可能在这方面提供有价值的信息。这一点也很重要 把重点放在分子变化上，这种变化可以在肿瘤前病变中检测到 而且可以作为临床靶点，不良反应最小，因为 通过消除烟草滥用初步预防与吸烟有关的癌症 对每个人来说，这可能不是一个现实的目标。我们建议对 “癌前”病变的全球DNA甲基化是一种重要的表观遗传学 更改需要验证，因为它在 癌症的发生及其通过营养改变其状态的可能性 干预。这项提案中要检验的主要假设是 全球DNA甲基化状态在“癌前”病变(增生， 人肺、喉和口腔的化生、异型增生和非典型增生 与甲基化相比，未患癌症的受试者更高 在患有癌症的受试者中检测到的相同“癌前”病变的状况 罹患癌症。为了验证这一假设，进行了一项回溯性的跟踪研究 将在被诊断为“肿瘤前期”的受试者中进行。 肺、喉或口腔的病变。被跟踪的受试者 临床上将进行至少三年的研究。那些开发了一种 将发生癌症事件的人与没有发生的人进行比较， 诊断的“癌前”病变的DNA整体甲基化程度 在底线。一种新开发和测试的免疫组织化学技术， 它测量完整和特定类型的全局甲基化程度 将被用来评估在拟议的 学习。

DESCRIPTION: (provided by Applicant) It is recognized that cigarette smoking is a common risk factor for the development of cancers of the lung, larynx and oral cavity. Although "pre-neoplastic" lesions are identified for these smoking related cancers, not all lesions become malignant and currently there is insufficient evidence to determine which features reliably predict malignant potential of such lesions. We hypothesize that the conventional histopathological examination of pre-neoplastic" lesions provides insufficient information on prognosis, but genetic and epigenetic alterations in these lesions may provide valuable information in this regard. It is also important to focus on molecular alterations, which can be detected in 'pre-neoplastic" lesions and could be clinically targeted with minimum adverse effects, since primary prevention of smoking related cancers by elimination of tobacco abuse may not be a realistic goal for everyone. We propose that alterations in global DNA methylation in "pre-neoplastic" lesions is an important epigenetic change to be validated because of its significance in the process of carcinogenesis and the possibility of changing its status by nutritional intervention. The primary hypothesis to be tested in this proposal is that global DNA methylation status in 'pre-neoplastic" lesions (hyperplasia, metaplasia, dysplasia and CIS) of the human lung, larynx and oral cavity of subjects who have not developed cancers is higher compared to the methylation status of the same "pre-neoplastic" lesions detected in subjects who have developed cancers. To test this hypothesis, a retrospective follow-up study will be conducted with subjects who were diagnosed with a "pre-neoplastic" lesion of the lung, larynx or oral cavity. Subjects who have been followed clinically for at least three years will be studied. Those who developed an incident cancer vvill be compared to those who did not, with respect to the degree of global methylation of DNA of the 'pre-neoplastic" lesions diagnosed at the baseline. A newly developed and tested immunohistochemical technique, which measures the degree of global methylation in intact and specific types of cells, will be used to evaluate global DNA methylation in the proposed study.