GENOMIC SCANNING IN ORAL CANCER

头颈癌（HNC）是世界上第六大最常见的癌症，因此是一个主要的公共卫生问题。现在已经确定癌症是一种细胞水平上的遗传疾病。遗传改变包括致癌基因的激活和抑癌基因的失活。尽管已经取得了实质性进展，但对这些癌症的发生、进展和复发的遗传机制仍然知之甚少。现在人们普遍认为，表观遗传改变（DNA甲基化）以及遗传变化对癌症的发展很重要。DNA甲基化在HNCs进展中的重要性尚不完全清楚。为了更好地了解头颈部鳞状细胞癌（HNSCC）中与这些事件相关的遗传和表观遗传事件，我们建议鉴定新的致癌基因和候选肿瘤抑制基因。我们的假设是，HNSCC的肿瘤发生与表观遗传变化有关，如启动子甲基化，导致RNA水平的特异性变化。我们计划使用限制性标记基因组扫描（RLGS）方法，该方法非常适合识别DNA甲基化模式的改变以及DNA扩增。目标是：(1)基于改变的DNA甲基化模式，利用RLGS识别新的扩增序列和肿瘤抑制候选区域；(2)构建ascii - ecorv阵列库，便于克隆。(3)候选肿瘤基因的克隆将集中在肿瘤中高频改变的区域。候选癌基因将在LOH和/pr DNA甲基化发生率高的染色体区域中确定。(4)最终目标是建立合适的诊断性生物标志物，可用于快速识别hnscc特异性改变。

Head and Neck cancers (HNC) are the sixth most common cancer in the world, and therefore are a major public health concern. It is now well- established that cancer is a genetic disease at the cellular level. Genetic alterations include the activation of oncogenes and inactivation of tumor suppressor genes. Although substantial progress has been made, still relatively little is known about the genetic mechanisms involved in initiation, progression, and recurrence of these cancers. It is now well accepted that epigenetic alterations (DNA methylation) as well as genetic changes are important for the development of cancer. The importance of DNA methylation in progression of HNCs is not completely understood. To gain a better understanding of the genetic and epigenetic events associated with these events in head and neck squamous cell carcinomas (HNSCC), we propose to identify novel oncogenes and candidate tumor suppressor genes. Our hypothesis is that tumorigenesis of HNSCC is associated with epigenetic changes e.g. promoter methylation, which results in specific changes at the RNA level. We are planning to use the Restriction Landmark Genomic Scanning (RLGS) method which is uniquely suited to identify altered DNA methylation patterns as well as DNA amplification. The goals are: (1) to use RLGS to identify novel amplified sequences and tumor suppressor candidate regions based on altered DNA methylation pattern; (2) the construction of an AscI-EcoRV arrayed library to facilitate the cloning. (3) The cloning of candidate cancer genes will focus on those areas that are altered at high frequency in the tumors. Candidate oncogenes will be identified in chromosomal regions with high incidences of LOH and/pr DNA methylation. (4) The final goal is the establishment of suitable diagnostic biomarkers, which can be used for rapid identification of HNSCC-specific alterations.