人类基因组的1p36区域是一个公认的抑癌基因热点区域，包含了TP73在内的多个经典抑癌基因。1p36的高频缺失是在多种肿瘤中普遍存在的遗传变异。随着抑癌基因岛概念的提出及逐步映证，研究者们相信1p36区段可能还存在未被发现的具有抑癌功能的基因。本项目将首次全面阐明一个新的1p36抑癌基因TUSC6在鼻咽癌和结直肠癌中的表达沉默机制、其生物学功能及抑癌的分子机理，完善位于1p36区域的抑癌基因谱，为理解1p36缺失在鼻咽癌和结直肠癌发生发展中的重要作用提供实验依据。本项目将证明启动子区甲基化导致TUSC6在肿瘤细胞中表达下调或沉默，并深入研究由此引起的异常信号转导及基因调控。另外，基础研究与转化研究相结合，评价TUSC6甲基化作为新型分子标志物的可能将为鼻咽癌和结直肠癌的早期诊断和预后判断提供新的思路。

The chromosome 1p36 region in the human genome is a well-known tumor suppressor gene (TSG) hot spot, which contains multiple classic TSGs such as TP73. The high frequency loss of 1p36 is a common genetic alteration in multiple tumors. With the emerging "cancer-gene island" theory being verified, it is believed that 1p36 region is likely to harbor gene(s) with anti-tumorigenic activity which has not been described yet. This project will investigate a novel 1p36 TSG, TUSC6, for its epigenetic silencing in Nasopharyngeal Carcinoma (NPC) and Colorectal Cancer (CRC), and further clarify its biological functions and molecular basis of tumor-suppression mediated by TUSC6. Thus, this study will add a new component to 1p36 TSG cluster, and provide experimental basis for elucidating the important role of 1p36 loss in the initiation and progression of NPC and CRC. We will confirm that the downregulation or silencing of TUSC6 in tumor cells is due to promoter CpG methylation, and further clarify abnormal signal transduction and gene regulation resulted from TUSC6 inactivation. In addition, for translational research, evaluation of TUSC6 methylation as an epigenetic biomarker will provide a new strategy for the early detection and prognosis prediction of NPC and CRC.