MYB-QKI Rearrangements in Angiocentric Glioma Drive Tumorigenicity through a Tripartite Mechanism

2nd Annual CBTTC Investigator Meeting, The Westin New Orleans Canal Place, New Orleans

May 25, 2016
Adam Resnick, PhD, The Children’s Hospital of Philadelphia


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.