在中国，黑色素瘤每年新发病例已经超过二万人；其中，近四分之一的亚型为亚裔人群“特有”的粘膜型黑色素瘤。与皮肤型相比，粘膜型黑色素瘤具有独特的基因组变异特征，诊疗难度高，预后极差，尚无标准治疗指南可循。本课题组前期研究发现，EZH2拷贝数在粘膜型黑色素瘤患者的肿瘤组织样本中显著扩增，且与患者不良预后相关；干扰或抑制EZH2的表达和活性均可以显著的抑制粘膜型黑色素瘤的体内外增殖能力；整合干扰EZH2后的表达谱数据和ENCODE数据分析发现，EZH2可能通过修饰H3K27me3介导CRTAC1的沉默。迄今，EZH2是否可以直接调控CRTAC1的表达以及CRTAC1是否参与肿瘤发生发展尚无报道。本项目拟进一步明确EZH2在粘膜型黑色素瘤中的功能机制, 探讨EZH2通过调控CRTAC1影响粘膜型黑色素瘤发生发展的作用机制，评估EZH2-CRTAC1作为粘膜型黑色素瘤的诊断指标和治疗靶点的临床意义。

There are more than 20,000 new cases annually in China. mucosal melanoma accounts for about 25% as a "unique" subtype of Mongolian . Compared with skin melanoma, mucosal melanoma has unique genomic variation characteristics for high difficulty in diagnosis and treatment, and poor prognosis and there is no treatment guide for this subtype of melanoma to follow currently. Our previous study found that copy number of EZH2 was significantly amplified in patients with mucosal melanoma, and high copy of EZH2 was associated with poor prognosis. Interfering or inhibiting the expression and activity of EZH2 can significantly inhibit the proliferation of mucosal melanoma in vivo and in vitro .Analysis of expression spectrum data and ENCODE data after interference with EZH2 revealed that EZH2 might inhibit CRTAC1 expression by modifying H3K27me3. However, whether EZH2 directly regulate CRTAC1 expression or is involved in tumorigenesis and development have not been reported. This project intends to further clarify the function of EZH2 in mucosal melanoma, to explore the mechanism by which EZH2 affects the occurrence and development of mucosal melanoma through the regulation of CRTAC1, and to evulate the clinical significance of EZH2-CRTAC1 as the diagnostic index and therapeutic target of mucosal melanoma.