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

Nat Genet
Authors
Keywords
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.

Year of Publication
2016
Journal
Nat Genet
Volume
48
Issue
3
Pages
273-82
Date Published
2016 Mar
ISSN
1546-1718
URL
DOI
10.1038/ng.3500
PubMed ID
26829751
PubMed Central ID
PMC4767685
Links
Grant list
R01 CA188228 / CA / NCI NIH HHS / United States
1R01NS091620 / NS / NINDS NIH HHS / United States
T32 HL007627 / HL / NHLBI NIH HHS / United States
P01 CA142536 / CA / NCI NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
P01CA142536 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
K08 NS087118 / NS / NINDS NIH HHS / United States
R01NS085336 / NS / NINDS NIH HHS / United States
R01 NS085336 / NS / NINDS NIH HHS / United States
K08NS087118 / NS / NINDS NIH HHS / United States
F30 CA192725 / CA / NCI NIH HHS / United States
F32 CA180653 / CA / NCI NIH HHS / United States