Tong Yiai, Merino Diana, Nimmervoll Birgit, Gupta Kirti, Wang Yong-Dong, Finkelstein David, Dalton James, Ellison David W, Ma Xiaotu, Zhang Jinghui, Malkin David, Gilbertson Richard J
Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Genetics and Genome Biology Program, The Hospital for Sick Children, Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1X8, Canada.
Cancer Cell. 2015 May 11;27(5):712-27. doi: 10.1016/j.ccell.2015.04.005.
Choroid plexus carcinomas (CPCs) are poorly understood and frequently lethal brain tumors with few treatment options. Using a mouse model of the disease and a large cohort of human CPCs, we performed a cross-species, genome-wide search for oncogenes within syntenic regions of chromosome gain. TAF12, NFYC, and RAD54L co-located on human chromosome 1p32-35.3 and mouse chromosome 4qD1-D3 were identified as oncogenes that are gained in tumors in both species and required for disease initiation and progression. TAF12 and NFYC are transcription factors that regulate the epigenome, whereas RAD54L plays a central role in DNA repair. Our data identify a group of concurrently gained oncogenes that cooperate in the formation of CPC and reveal potential avenues for therapy.
脉络丛癌(CPCs)是一种了解甚少且通常致命的脑肿瘤,治疗选择有限。我们利用该疾病的小鼠模型和大量人类CPCs样本,在染色体获得的同线区域内进行了跨物种全基因组致癌基因搜索。位于人类染色体1p32 - 35.3和小鼠染色体4qD1 - D3上的TAF12、NFYC和RAD54L被鉴定为致癌基因,在两个物种的肿瘤中均有获得,且是疾病起始和进展所必需的。TAF12和NFYC是调节表观基因组的转录因子,而RAD54L在DNA修复中起核心作用。我们的数据鉴定出一组在CPC形成过程中协同作用的同时获得的致癌基因,并揭示了潜在的治疗途径。