Mohankumar Kumarasamypet M, Currle David S, White Elsie, Boulos Nidal, Dapper Jason, Eden Christopher, Nimmervoll Birgit, Thiruvenkatam Radhika, Connelly Michele, Kranenburg Tanya A, Neale Geoffrey, Olsen Scott, Wang Yong-Dong, Finkelstein David, Wright Karen, Gupta Kirti, Ellison David W, Thomas Arzu Onar, Gilbertson Richard J
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nat Genet. 2015 Aug;47(8):878-87. doi: 10.1038/ng.3323. Epub 2015 Jun 15.
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.
癌症的特征是存在非随机的染色体拷贝数改变，这些改变可能包含癌基因和肿瘤抑制基因（TSGs）。受影响的基因座通常很大，这使得很难确定哪些基因在驱动癌症。在此，我们报告了一项跨物种体内筛选，涉及位于室管膜瘤28种复发性染色体改变区域内的84个候选癌基因和39个候选肿瘤抑制基因。通过一系列小鼠模型，我们验证了8个新的室管膜瘤癌基因和10个新的室管膜瘤肿瘤抑制基因，这些基因汇聚于少数细胞功能，包括囊泡运输、DNA修饰和胆固醇生物合成，将这些确定为潜在的新治疗靶点。
