MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
Pratiti BandopadhayayLori A RamkissoonPayal JainGuillaume BergtholdJeremiah WalaRhamy ZeidSteven E SchumacherLaura UrbanskiRyan O'RourkeWilliam J GibsonKristine PeltonShakti H RamkissoonHarry J HanYuankun ZhuNamrata ChoudhariAmanda SilvaKatie BoucherRosemary E HennYun Jee KangDavid S KnoffBrenton R PaolellaAdrianne Gladden-YoungPascale VarletMelanie PagesPeleg M HorowitzAlexander FederationHayley MalkinAdam A TracySara SeepoMatthew DucarPaul Van HummelenMariarita SantiAnna Maria BuccolieroMirko ScagnetDaniel C BowersCaterina GianniniStephanie PugetCynthia HawkinsUri TaboriAlmos KleknerLaszlo BognarPeter C BurgerCharles EberhartFausto J RodriguezD Ashley HillSabine MuellerDaphne A Haas-KoganJoanna J PhillipsSandro SantagataCharles D StilesJames E BradnerNada JabadoAlon GorenJacques GrillAzra H LigonLiliana GoumnerovaAngela J WaandersPhillip B StormMark W KieranKeith L LigonRameen BeroukhimAdam C ResnickPublished in: Nature genetics (2016)
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.