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: 6201812
• 负责人: JAMES C LANG
• 金额: $ 15.83万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6201812
• 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，世界各地都在尝试分析……的分子生物学