血管中心性胶质瘤中的MYB-QKI重排通过三方机制驱动肿瘤发生。
MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
作者信息
Bandopadhayay Pratiti, Ramkissoon Lori A, Jain Payal, Bergthold Guillaume, Wala Jeremiah, Zeid Rhamy, Schumacher Steven E, Urbanski Laura, O'Rourke Ryan, Gibson William J, Pelton Kristine, Ramkissoon Shakti H, Han Harry J, Zhu Yuankun, Choudhari Namrata, Silva Amanda, Boucher Katie, Henn Rosemary E, Kang Yun Jee, Knoff David, Paolella Brenton R, Gladden-Young Adrianne, Varlet Pascale, Pages Melanie, Horowitz Peleg M, Federation Alexander, Malkin Hayley, Tracy Adam A, Seepo Sara, Ducar Matthew, Van Hummelen Paul, Santi Mariarita, Buccoliero Anna Maria, Scagnet Mirko, Bowers Daniel C, Giannini Caterina, Puget Stephanie, Hawkins Cynthia, Tabori Uri, Klekner Almos, Bognar Laszlo, Burger Peter C, Eberhart Charles, Rodriguez Fausto J, Hill D Ashley, Mueller Sabine, Haas-Kogan Daphne A, Phillips Joanna J, Santagata Sandro, Stiles Charles D, Bradner James E, Jabado Nada, Goren Alon, Grill Jacques, Ligon Azra H, Goumnerova Liliana, Waanders Angela J, Storm Phillip B, Kieran Mark W, Ligon Keith L, Beroukhim Rameen, Resnick Adam C
机构信息
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
出版信息
Nat Genet. 2016 Mar;48(3):273-82. doi: 10.1038/ng.3500. Epub 2016 Feb 1.
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 that 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. To our knowledge, this represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor.
血管中心性胶质瘤是一类未知复发性遗传驱动因素的儿童低级别胶质瘤（PLGGs）。我们对来自249例PLGGs（包括19例血管中心性胶质瘤）的新数据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中一个特定且唯一的候选驱动事件。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：通过截短激活MYB、增强子易位驱动异常的MYB-QKI表达以及肿瘤抑制因子QKI的半合子缺失。据我们所知，这代表了单个驱动重排在肿瘤中通过三种遗传和表观遗传机制同时转化细胞的首个实例。
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