MYB-QKI fusion: A novel alteration that may define and drive pediatric angiocentric glioma

Angiiocentric glioma

Angiocentric glioma is a rare form of pediatric low-grade gliomas (PLGG), first described in 2005, that arises in the cerebral cortex and shares histological features of astrocytomas and ependymomas. Until now, nothing was known of the genetic events underlying this tumor type. In a recent study published in Nature Genetics, Bhandopadhayay et al (see reference below) used whole genome sequencing and/or RNAseq to show that all seven angiocentric gliomas in their sample set harbored rearrangements in MYB, the most common being intrachromosomal deletions resulting in MYB-QKI gene fusions. QKI encodes the RNA-binding protein Quaking, which has been previously established as a tumor suppressor in glioblastoma. Analysis of 12 additional FFPE angiocentric glioma specimens revealed that all of these had alterations in MYB, with the MYB-QKI alteration being confirmed in six cases. The MYB-QKI gene fusion was not observed in any other PLGGs in the panel and therefore may specifically define angiocentric glioma. The MYB-QKI fusion protein was shown by mechanistic studies to drive expression of pro-oncogenic target genes. These data strongly support the concepts that MYB-QKI fusions define angiogentric glioma and act as the oncogenic driver mutation in this tumor.

This post is adapted from "Highlights from the Literature", edited by Kenneth Aldape in the journal Neuro-Oncology 18(6), 761–763, 2016

Reference:
Bhandopadhayay P, Ramkissoon LA, Jain P, et al. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism. Nat Genet 2016;48(3):273–282.