Prognostic Significance of Altered DNA Methylation

描述：（由申请人提供）众所周知，吸烟 是导致肺癌、喉癌和其他癌症的常见危险因素。 口腔 虽然“肿瘤前”病变被确定为这些 吸烟相关的癌症，并不是所有的病变都变成恶性的， 没有足够的证据来确定哪些特征可以可靠地预测 这种病变的恶性潜力。 我们假设传统的 肿瘤前病变的组织病理学检查提供了不充分的 预后的信息，但在这些遗传和表观遗传改变， 在这方面，病变可以提供有价值的信息。 也很重要 重点关注分子改变，这可以在“肿瘤前” 病变，并可以在临床上靶向最小的不良反应，因为 通过消除烟草滥用对与吸烟有关的癌症进行初级预防 可能不是每个人都能实现的目标。 我们建议， “肿瘤前”病变中的整体DNA甲基化是一种重要的表观遗传 由于其在以下过程中的重要性， 致癌作用和通过营养改变其状态的可能性 干预本提案中要检验的主要假设是， “肿瘤前”病变（增生， 上皮化生、发育不良和CIS）的人肺、喉和口腔的 未患癌症的受试者与未患癌症的受试者相比， 受试者中检测到的相同“肿瘤前”病变的状态 患上了癌症 为了验证这一假设，一项回顾性随访研究 将在诊断为“肿瘤前”的受试者中进行 肺、喉或口腔的病变。 已随访的受试者 临床研究至少三年。 那些开发了 癌症事件将与那些没有的人进行比较，就 诊断的“肿瘤前”病变的DNA整体甲基化程度 在基线上。 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整体甲基化程度， 细胞，将被用来评估全球DNA甲基化的建议， study.

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.