REGULATORY AND NOVEL GENES IN DEVELOPMENT OF ORAL CANCER

口腔癌发生过程中的调控基因和新基因

• 批准号: 6104960
• 负责人: JAMES C LANG
• 金额: --
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104960
• 关键词: cancer prevention; early diagnosis; gene deletion mutation; genetic markers; human tissue; loss of heterozygosity; neoplasm /cancer diagnosis; neoplasm /cancer genetics; oncogenes; oral leukoplakia; oral mucosa; oral pharyngeal neoplasm; point mutation; preneoplastic state; squamous cell carcinoma; tumor suppressor genes

Attempts are now underway worldwide to analyse the molecular biology of cancer causation, specifically to identify the genes whose functions are compromised by mutation or otherwise during cancer development. The rationale for this approach is that such knowledge will aid not only cancer treatment regimes, but also prevention and early detection of cancer. As a corollary, it is also important to examine pre-malignant tissues for such altered gene function. Recent data from our laboratory has shown that the oncogene cyclin D1 and the tumor suppressor gene p16 are frequently altered in SCC. Studies of loss of heterozygosity (LOH) in SCC of the head and neck suggest involvement of other, as yet unidentified genes in the disease. The Specific Aims of this proposal are designed to: First, determine the frequency and nature of genetic changes which occur in oncogene cyclin D1 and tumor suppressor gene p16 in SCC and investigate the hypothesis that changes to these genes may also be present in oral pre-malignant lesions (leukoplakia and/or erythroplakia) capable of progression to SCC. Second, identify other, novel genes expressed in normal oral mucosa but absent from SCC, since such genes may potentially be tumor suppressor genes or be important markers for disease progression. Specific Aim 1 will be achieved by analysis of a sample population comprising a total of 100 SCC specimens (50 oral cavity and 50 larynx/pharynx) and matched normal tissue. Specific Aim 2 will be achieved by comparative analysis of gene expression in positive neck nodes derived from oral SCC and matched tissue derived from normal oral mucosa. Nodal tissue will be used in preference to tissues from primary tumors since usage will preclude tumor sample contamination with normal oral epithelium. Additionally, we have observed a preliminary association between the category of alteration to the p16 gene (point mutation of deletion) and tumor site (oral cavity or larynx/pharynx respectively). One mutational status of p16 in the above 100 SCC is established, data will be analysed by statistical methods to determine whether a positive correlation between tumor site and category of mutation exists.

目前全世界都在尝试分析 癌症病因，特别是识别功能不同的基因 在癌症发展过程中受到突变或其他因素的影响。的 这种做法的理由是，这种知识不仅有助于 癌症治疗制度，而且预防和早期发现 癌作为一个推论，检查癌前病变也很重要。 这种基因功能的改变。我们实验室的最新数据 癌基因细胞周期蛋白D1和肿瘤抑制基因p16 在SCC中经常发生改变。中国汉族人群的杂合性缺失（洛）研究 头颈部鳞状细胞癌提示有其他尚未确定的病变 疾病中的基因。本提案的具体目标是： 首先，确定发生的遗传变化的频率和性质 癌基因cyclin D1和抑癌基因p16在鳞状细胞癌中表达及意义 假设这些基因的变化也可能存在于口腔中， 癌前病变（白斑病和/或红斑病）， 进展为SCC。第二，鉴定其他新的基因表达， 正常口腔粘膜，但不存在SCC，因为这些基因可能 是肿瘤抑制基因或疾病进展的重要标志物。 具体目标1将通过分析样本人群实现 包括总共100个SCC标本（50个口腔和50个口腔）， 喉/咽）和匹配的正常组织。具体目标2将实现 通过比较分析阳性颈淋巴结中的基因表达， 来自口腔SCC和来自正常口腔粘膜的匹配组织。节点 组织将优先于来自原发性肿瘤的组织使用， 使用将排除肿瘤样品与正常口服 上皮此外，我们还观察到一种初步的关联， 在p16基因改变的类别（p16基因的点突变）之间， 缺失）和肿瘤部位（分别为口腔或喉/咽）。一 以上100例SCC中p16突变状态的建立，数据将 通过统计方法进行分析，以确定是否为阳性 肿瘤部位和突变类型之间存在相关性。