Child's Nervous System

, Volume 27, Issue 1, pp 87–94

IDH1 mutations are common in malignant gliomas arising in adolescents: a report from the Children’s Oncology Group

  • Ian F. Pollack
  • Ronald L. Hamilton
  • Robert W. Sobol
  • Marina N. Nikiforova
  • Maureen A. Lyons-Weiler
  • William A. LaFramboise
  • Peter C. Burger
  • Daniel J. Brat
  • Marc K. Rosenblum
  • Emiko J. Holmes
  • Tianni Zhou
  • Regina I. Jakacki
  • for the Children’s Oncology Group
Original Paper

Abstract

Purpose

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.

Experimental design

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.

Keywords

Anaplastic glioma Childhood Glioblastoma IDH 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Ian F. Pollack
    • 1
  • Ronald L. Hamilton
    • 2
  • Robert W. Sobol
    • 3
  • Marina N. Nikiforova
    • 2
  • Maureen A. Lyons-Weiler
    • 5
  • William A. LaFramboise
    • 2
    • 5
  • Peter C. Burger
    • 6
  • Daniel J. Brat
    • 7
  • Marc K. Rosenblum
    • 8
  • Emiko J. Holmes
    • 9
  • Tianni Zhou
    • 9
  • Regina I. Jakacki
    • 4
  • for the Children’s Oncology Group
  1. 1.Department of NeurosurgeryChildren’s Hospital of Pittsburgh, University of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Department of Pharmacology and Chemical BiologyHillman Cancer Center, University of Pittsburgh Cancer Institute and University of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of PediatricsChildren’s Hospital of Pittsburgh, University of Pittsburgh School of MedicinePittsburghUSA
  5. 5.The Clinical Genomics FacilityUniversity of Pittsburgh School of MedicinePittsburghUSA
  6. 6.Department of PathologyJohns Hopkins UniversityBaltimoreUSA
  7. 7.Department of PathologyEmory UniversityAtlantaUSA
  8. 8.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  9. 9.Statistical and Data CenterThe Children’s Oncology GroupArcadiaUSA

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