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

Nature Genetics
Pratiti BandopadhayayAdam C Resnick

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.

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Methods Mentioned

BETA
RNA-seq
immunoprecipitation
transfection
xenografts
exome sequencing
PCR
Assay
ChIP
ChIP-seq

Software Mentioned

Mutect
MACS
Active Motif
IGV
Mutsig
Firehose
BreakPointer
ImageJ
Picard
PRADA ( Pipeline for RNA - sequencing Data Analysis )

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