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Genomic Analysis of Pediatric Low Grade Gliomas
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Keith L. Ligon, MD, PhD,  
Project

About This Dataset
Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from mutations or duplications in the BRAF kinase in specific subclasses, few genetic driver events are known. Diffuse PLGGs compose a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. These tumors are particularly poorly understood. We performed high-resolution copy-number analysis of 44 diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gains, was observed in 28% of diffuse astrocytoma WHO grade II (DA2) and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene MYB on 6q23.3. Whole genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Two truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth when expressed in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas.
Core Data Elements
Number of Cases
1
Case Sex
Female (1)
Case Age At Diagnosis
0 to 4 years (1)
Case Race
Not Reported (1)
Case Ethnicity
Not Reported (1)
Case Disease Diagnosis
Diffuse Pediatric Low-Grade Gliomas (1)
Number of Samples
2
Sample Anatomic Site
Blood (1); Left Parietal Lobe (1)
Sample Is Normal
Yes (1); No (1)
Additional Data Elements
DBGAP STUDY IDENTIFIER
GEO STUDY IDENTIFIER
Grant Information
P01CA142536
Therapeutic Opportunities for Pediatric Astrocytoma
Published In
https://doi.org/10.1073/pnas.1300252110
Charts
Female (1)
1Female