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MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.

ABSTRACT: 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.

SUBMITTER: Bandopadhayay P 

PROVIDER: S-EPMC4767685 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.

Bandopadhayay Pratiti P   Ramkissoon Lori A LA   Jain Payal P   Bergthold Guillaume G   Wala Jeremiah J   Zeid Rhamy R   Schumacher Steven E SE   Urbanski Laura L   O'Rourke Ryan R   Gibson William J WJ   Pelton Kristine K   Ramkissoon Shakti H SH   Han Harry J HJ   Zhu Yuankun Y   Choudhari Namrata N   Silva Amanda A   Boucher Katie K   Henn Rosemary E RE   Kang Yun Jee YJ   Knoff David D   Paolella Brenton R BR   Gladden-Young Adrianne A   Varlet Pascale P   Pages Melanie M   Horowitz Peleg M PM   Federation Alexander A   Malkin Hayley H   Tracy Adam A AA   Seepo Sara S   Ducar Matthew M   Van Hummelen Paul P   Santi Mariarita M   Buccoliero Anna Maria AM   Scagnet Mirko M   Bowers Daniel C DC   Giannini Caterina C   Puget Stephanie S   Hawkins Cynthia C   Tabori Uri U   Klekner Almos A   Bognar Laszlo L   Burger Peter C PC   Eberhart Charles C   Rodriguez Fausto J FJ   Hill D Ashley DA   Mueller Sabine S   Haas-Kogan Daphne A DA   Phillips Joanna J JJ   Santagata Sandro S   Stiles Charles D CD   Bradner James E JE   Jabado Nada N   Goren Alon A   Grill Jacques J   Ligon Azra H AH   Goumnerova Liliana L   Waanders Angela J AJ   Storm Phillip B PB   Kieran Mark W MW   Ligon Keith L KL   Beroukhim Rameen R   Resnick Adam C AC  

Nature genetics 20160201 3

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 aberra  ...[more]

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