Molecular pathogenesis of Merkel cell carcinoma

默克尔细胞癌的分子发病机制

• 批准号: 8938090
• 负责人: Isaac Brownell
• 金额: $ 54.49万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8938090
• 关键词: Animal Model; Biological Assay; Cancer cell line; Cell Culture Techniques; Chromosome abnormality; Data; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Gene Expression; Gene Mutation; Genetic; Goals; Human; In Vitro; Merkel Cells; Merkel cell carcinoma; Modification; Molecular; Mus; Mutation; Oncogenic; Pathogenesis; Pathway interactions; Sampling; Skin; Testing; Work; Xenograft procedure; genome-wide; in vivo; mouse model; pre-clinical; prevent; prognostic; therapeutic target; tumor

To identify genetic alterations present in Merkel cell carcinoma, we have conducted molecular analyses of human tumors across multiple genome-wide platforms to assay gene expression, identify gene mutations and characterize chromosomal alterations. These data are being analyzed to identify key driver alterations for this tumor. We are also generating mice where oncogenic modifications are carried out in specific skin lineages in an attempt to transform Merkel cells in vivo. In addition, we are developing and characterizing cancer cell lines of Merkel cell carcinoma for in vitro and xenograft studies. Finally we are conducting a genetic knockdown screen to identify pathways important for tumor survival.

为了鉴定默克尔细胞癌中存在的遗传改变，我们已经对跨多个基因组平台的人类肿瘤进行了分子分析，以测定基因表达，鉴定基因突变并表征染色体改变。正在分析这些数据，以识别该肿瘤的关键驱动因素改变。我们还生成小鼠，在特定的皮肤谱系中进行致癌修饰，以尝试在体内转化默克尔细胞。此外，我们正在开发和表征默克尔细胞癌的癌细胞系，用于体外和异种移植研究。最后，我们正在进行遗传敲低筛查，以识别对肿瘤存活重要的途径。