- MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.
Nature genetics (2016-02-02)
Pratiti Bandopadhayay, Lori A Ramkissoon, Payal Jain, Guillaume Bergthold, Jeremiah Wala, Rhamy Zeid, Steven E Schumacher, Laura Urbanski, Ryan O'Rourke, William J Gibson, Kristine Pelton, Shakti H Ramkissoon, Harry J Han, Yuankun Zhu, Namrata Choudhari, Amanda Silva, Katie Boucher, Rosemary E Henn, Yun Jee Kang, David Knoff, Brenton R Paolella, Adrianne Gladden-Young, Pascale Varlet, Melanie Pages, Peleg M Horowitz, Alexander Federation, Hayley Malkin, Adam A Tracy, Sara Seepo, Matthew Ducar, Paul Van Hummelen, Mariarita Santi, Anna Maria Buccoliero, Mirko Scagnet, Daniel C Bowers, Caterina Giannini, Stephanie Puget, Cynthia Hawkins, Uri Tabori, Almos Klekner, Laszlo Bognar, Peter C Burger, Charles Eberhart, Fausto J Rodriguez, D Ashley Hill, Sabine Mueller, Daphne A Haas-Kogan, Joanna J Phillips, Sandro Santagata, Charles D Stiles, James E Bradner, Nada Jabado, Alon Goren, Jacques Grill, Azra H Ligon, Liliana Goumnerova, Angela J Waanders, Phillip B Storm, Mark W Kieran, Keith L Ligon, Rameen Beroukhim, Adam C Resnick
PMID26829751
RÉSUMÉ
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.
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