A distinct spectrum of copy number aberrations in pediatric high-grade gliomas.
OBJECTIVE
As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors.


METHODS
We carried out copy number profiling by array comparative genomic hybridization using a 32K bacterial artificial chromosome platform on 63 formalin-fixed paraffin-embedded cases of high-grade glioma arising in children and young people (<23 years).


RESULTS
The genomic profiles of these tumors could be subclassified into four categories: those with stable genomes, which were associated with a better prognosis; those with aneuploid and those with highly rearranged genomes; and those with an amplifier genotype, which had a significantly worse clinical outcome. Independent of this was a clear segregation of cases with 1q gain (more common in children) from those with concurrent 7 gain/10q loss (a defining feature of adults). Detailed mapping of all the amplification and deletion events revealed numerous low-frequency amplifications, including IGF1R, PDGFRB, PIK3CA, CDK6, CCND1, and CCNE1, and novel homozygous deletions encompassing unknown genes, including those at 5q35, 10q25, and 22q13. Despite this, aberrations targeting the "core signaling pathways" in adult glioblastomas are significantly underrepresented in the pediatric setting.


CONCLUSIONS
These data highlight that although there are overlaps in the genomic events driving gliomagenesis of all ages, the pediatric disease harbors a distinct spectrum of copy number aberrations compared with adults.
Bax
Dorine A
DA
Section of Paediatric Oncology, The Institute of Cancer Research, Royal Marsden Hospital, Sutton, United Kingdom.
Mackay
Alan
A
Little
Suzanne E
SE
Carvalho
Diana
D
Viana-Pereira
Marta
M
Tamber
Narinder
N
Grigoriadis
Anita E
AE
Ashworth
Alan
A
Reis
Rui M
RM
Ellison
David W
DW
Al-Sarraj
Safa
S
Hargrave
Darren
D
Jones
Chris
C
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005784:Gene Amplification; D017353:Gene Deletion; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans