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

Bandopadhayay, Pratiti and Ramkissoon, Lori A and Jain, Payal and Bergthold, Guillaume and Wala, Jeremiah and Zeid, Rhamy and Schumacher, Steven E and Urbanski, Laura and O'Rourke, Ryan and Gibson, William J and Pelton, Kristine and Ramkissoon, Shakti H and Han, Harry J and Zhu, Yuankun and Choudhari, Namrata and Silva, Amanda and Boucher, Katie and Henn, Rosemary E and Kang, Yun Jee and Knoff, David and Paolella, Brenton R and Gladden-Young, Adrianne and Varlet, Pascale and Pages, Melanie and Horowitz, Peleg M and Federation, Alexander and Malkin, Hayley and Tracy, Adam A and Seepo, Sara and Ducar, Matthew and Van Hummelen, Paul and Santi, Mariarita and Buccoliero, Anna Maria and Scagnet, Mirko and Bowers, Daniel C and Giannini, Caterina and Puget, Stephanie and Hawkins, Cynthia and Tabori, Uri and Klekner, Almos and Bognar, Laszlo and Burger, Peter C and Eberhart, Charles and Rodriguez, Fausto J and Hill, D Ashley and Mueller, Sabine and Haas-Kogan, Daphne A and Phillips, Joanna J and Santagata, Sandro and Stiles, Charles D and Bradner, James E and Jabado, Nada and Goren, Alon and Grill, Jacques and Ligon, Azra H and Goumnerova, Liliana and Waanders, Angela J and Storm, Phillip B and Kieran, Mark W and Ligon, Keith L and Beroukhim, Rameen and Resnick, Adam C (2016) MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nature Genetics, 48 (3). pp. 273-282. ISSN 1546-1718

Text MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.pdf Restricted to Repository staff only Download (2MB) | Request a copy

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.

Actions (login required)

Edit Item