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

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 KnoffBrenton 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 Jae Waanders, Phillip B. Storm, Mark W. Kieran, Keith L. Ligon, Rameen Beroukhim*, Adam C. Resnick

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

169 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalNature Genetics
Issue number3
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Genetics


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