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.
MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism / Bandopadhayay P.; Ramkissoon L.A.; Jain P.; Bergthold G.; Wala J.; Zeid R.; Schumacher S.E.; Urbanski L.; O'Rourke R.; Gibson W.J.; Pelton K.; Ramkissoon S.H.; Han H.J.; Zhu Y.; Choudhari N.; Silva A.; Boucher K.; Henn R.E.; Kang Y.J.; Knoff D.; Paolella B.R.; Gladden-Young A.; Varlet P.; Pages M.; Horowitz P.M.; Federation A.; Malkin H.; Tracy A.A.; Seepo S.; Ducar M.; Van Hummelen P.; Santi M.; Buccoliero A.M.; Scagnet M.; Bowers D.C.; Giannini C.; Puget S.; Hawkins C.; Tabori U.; Klekner A.; Bognar L.; Burger P.C.; Eberhart C.; Rodriguez F.J.; Hill D.A.; Mueller S.; Haas-Kogan D.A.; Phillips J.J.; Santagata S.; Stiles C.D.; Bradner J.E.; Jabado N.; Goren A.; Grill J.; Ligon A.H.; Goumnerova L.; Waanders A.J.; Storm P.B.; Kieran M.W.; Ligon K.L.; Beroukhim R.; Resnick A.C.. - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 48:3(2016), pp. 273-282. [10.1038/ng.3500]
MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism
Giannini C.;
2016
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
