IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children's Oncology Group.
OBJECTIVE
Recent studies have demonstrated a high frequency of IDH mutations in adult "secondary" malignant gliomas arising from preexisting lower grade lesions, often in young adults, but not in "primary" gliomas. Because pediatric malignant gliomas share some molecular features with adult secondary gliomas, we questioned whether a subset of these tumors also exhibited IDH mutations.


METHODS
We examined the frequency of IDH mutations, using real-time polymerase chain reaction and sequencing analysis, in a cohort of 43 pediatric primary malignant gliomas treated on the Children's Oncology Group ACNS0423 study. The relationship between IDH mutations and other molecular and clinical factors, and outcome, was evaluated.


RESULTS
IDH1 mutations were observed in 7 of 43 (16.3%) tumors; no IDH2 mutations were observed. A striking age association was apparent in that mutations were noted in 7 of 20 tumors (35%) from children ≥14 years, but in 0 of 23 (0%) younger children (p = 0.0024). No association was observed with clinical factors other than age. One-year event-free survival was 86 ± 15% in the IDH-mutated group versus 64 ± 8% in the non-mutated group (p = 0.03, one-sided logrank test). One-year overall survival was 100% in patients with mutations versus 81 ± 6.7% in those without mutations (p = 0.035, one-sided logrank test).


CONCLUSIONS
IDH1 mutations are common in malignant gliomas in older children, suggesting that a subset of these lesions may be biologically similar to malignant gliomas arising in younger adults and may be associated with a more favorable prognosis.
Pollack
Ian F
IF
Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. ian.pollack@chp.edu
Hamilton
Ronald L
RL
Sobol
Robert W
RW
Nikiforova
Marina N
MN
Lyons-Weiler
Maureen A
MA
LaFramboise
William A
WA
Burger
Peter C
PC
Brat
Daniel J
DJ
Rosenblum
Marc K
MK
Holmes
Emiko J
EJ
Zhou
Tianni
T
Jakacki
Regina I
RI
D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002681:China; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human