REGULATORY AND NOVEL GENES IN DEVELOPMENT OF ORAL CANCER

目前正在全世界范围内尝试分析这种病毒的分子生物学。 癌症病因，特别是识别其功能是什么的基因 在癌症发展过程中受到突变或其他因素的影响。这个 这种方法的基本原理是，这种知识不仅有助于 癌症治疗方案，但也预防和早期发现 癌症。作为推论，检查癌前病变也很重要。 这种改变基因功能的组织。我们实验室的最新数据 研究表明，癌基因细胞周期蛋白d1和抑癌基因p16 在鳞状细胞癌中经常改变。中国人杂合性缺失(LOH)研究 头部和颈部的鳞状细胞癌提示有其他尚未确定的病变。 疾病中的基因。这项建议的具体目的是： 首先，确定发生遗传变化的频率和性质 癌基因细胞周期蛋白d1和抑癌基因p16在鳞癌中的表达及意义 假设这些基因的变化也可能出现在口腔中 癌前病变(白斑和/或红斑)能够 进展为鳞癌。第二，找出其他新的基因。 正常口腔黏膜，但在鳞状细胞癌中缺失，因为这些基因可能 是肿瘤抑制基因，还是疾病进展的重要标志。 具体目标1将通过分析样本总体来实现 包括100个鳞癌标本(50个口腔标本和50个口腔标本 喉/咽)和匹配的正常组织。将实现具体目标2 通过对阳性颈淋巴结中基因表达的比较分析 取自口腔鳞癌和来自正常口腔粘膜的配对组织。节点 组织将优先用于原发肿瘤的组织，因为 使用将避免肿瘤样本与正常口腔污染 上皮组织。此外，我们观察到了一个初步的关联 在p16基因改变的类别(点突变 缺失)和肿瘤部位(分别为口腔或喉/咽)。一 P16在100以上鳞癌中的突变状态被确立，数据将被 通过统计方法分析，确定是否存在阳性 肿瘤部位与突变类型之间存在相关性。

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.