MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
复制标题
MYB-QKI重排在血管中心神经胶质瘤中通过三方机制驱动肿瘤性。
DOI：
10.1038/ng.3500
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发表时间：
2016-03
期刊：
影响因子：
30.8
通讯作者：
Resnick AC
中科院分区：
文献类型：
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作者：
Bandopadhayay P;Ramkissoon LA;Jain P;Bergthold G;Wala J;Zeid R;Schumacher SE;Urbanski L;O'Rourke R;Gibson WJ;Pelton K;Ramkissoon SH;Han HJ;Zhu Y;Choudhari N;Silva A;Boucher K;Henn RE;Kang YJ;Knoff D;Paolella BR;Gladden-Young A;Varlet P;Pages M;Horowitz PM;Federation A;Malkin H;Tracy AA;Seepo S;Ducar M;Van Hummelen P;Santi M;Buccoliero AM;Scagnet M;Bowers DC;Giannini C;Puget S;Hawkins C;Tabori U;Klekner A;Bognar L;Burger PC;Eberhart C;Rodriguez FJ;Hill DA;Mueller S;Haas-Kogan DA;Phillips JJ;Santagata S;Stiles CD;Bradner JE;Jabado N;Goren A;Grill J;Ligon AH;Goumnerova L;Waanders AJ;Storm PB;Kieran MW;Ligon KL;Beroukhim R;Resnick AC
血管中心性胶质瘤是儿科低级别胶质瘤（PLGGs），没有已知的复发遗传驱动因素。我们对249例PLGGs（包括19例血管中心性胶质瘤）的最新和已发表数据进行了基因组分析。我们确定MYB-QKI融合是血管中心性胶质瘤的一个特定的单一候选驱动事件。体外和体内功能研究表明，MYB-QKI重排通过三种机制促进肿瘤发生：MYB被截断激活，增强子易位驱动MYB-QKI异常表达，以及肿瘤抑制因子QKI的半合子缺失。这代表了肿瘤中单个驱动重排同时通过三种遗传和表观遗传机制转化细胞的第一个例子。
Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs including 19 Angiocentric Gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in Angiocentric Gliomas. In vitro and in vivo functional studies show MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of the tumor suppressor QKI. This represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor.