GENOMIC SCANNING IN ORAL CANCER

头颈部癌症(HNC)是世界上第六大常见癌症，因此是一个主要的公共卫生问题。癌症是细胞水平上的一种遗传性疾病，这一点现在已经得到了充分的证实。基因改变包括癌基因的激活和肿瘤抑制基因的失活。虽然已经取得了实质性的进展，但对这些癌症的发生、发展和复发所涉及的遗传机制仍然知之甚少。表观遗传改变(DNA甲基化)以及基因改变对癌症的发展是重要的，这一点现在得到了广泛的接受。DNA甲基化在HNC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学事件，我们建议识别新的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学变化有关，例如启动子甲基化，这导致了RNA水平的特定变化。我们计划使用限制性地标基因组扫描(RLGS)方法，它是唯一适合于识别DNA甲基化模式改变和DNA扩增的方法。其目的是：(1)利用RLGS根据DNA甲基化模式的改变来鉴定新的扩增序列和抑癌候选区域；(2)构建ASCI-EcoRV阵列文库，以便于克隆。(3)候选癌基因的克隆将集中在肿瘤中改变频率较高的区域。候选癌基因将被确定在DNA甲基化和/或杂合性缺失的高发区域。(4)最终目标是建立合适的诊断生物标记物，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.