Authors: 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 et al.
Summary:
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.
Source:
Nature Genetics; 02/01/16