Acta Neuropathologica

, Volume 131, Issue 2, pp 299–307 | Cite as

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

  • Alberto BroniscerEmail author
  • Omar Chamdine
  • Scott Hwang
  • Tong Lin
  • Stanley Pounds
  • Arzu Onar-Thomas
  • Sheila Shurtleff
  • Sariah Allen
  • Amar Gajjar
  • Paul Northcott
  • Brent A. Orr
Original Paper


Gliomatosis cerebri (GC), a rare and deadly CNS neoplasm characterized by involvement of at least three cerebral lobes, predominantly affects adults. While a few small series have reported its occurrence in children, little is known about the molecular characteristics of pediatric GC. We reviewed clinical, radiological, and histological features of pediatric patients with primary GC treated at our institution over 15 years. Targeted sequencing of mutational hotspots in H3F3A, IDH1/2, and BRAF, and genome-wide analysis of DNA methylation and copy number abnormalities was performed in available tumors. Thirty-two patients [23 (72 %) with type 1 and 9 (28 %) with type 2 GC] were identified. Median age at diagnosis was 10.2 years (range 1.5–19.1). A median of 4 cerebral lobes (range 3–8) was affected at diagnosis. In addition, symmetrical bithalamic involvement was observed in 9 (28 %) patients. Twenty-two patients (69 %) had an anaplastic astrocytoma. Despite aggressive therapy, only two patients younger than 3 years at diagnosis are long-term survivors. Clustering analysis of methylation array data from 18 cases classified tumors as IDH (n = 3, 17 %), G34 (n = 4, 22 %), mesenchymal (n = 3, 17 %), and RTK I ‘PDGFRA’ (n = 8, 44 %). No tumors were classified as K27 subgroup. PDGFRA was the most commonly amplified oncogene in 4 of 22 tumors (18 %). H3F3A p.G34 occurred in all cases classified as G34. Two of 3 cases in the IDH subgroup had IDH1 p.R132H. No H3F3A p.K27 M, IDH2 p.R172, or BRAF p.V600E mutations were observed. There was a trend towards improved survival in the IDH subgroup (P = 0.056). Patients with bithalamic involvement had worse outcomes (P = 0.019). Despite some overlap, the molecular features of pediatric GC are distinct from its adult counterpart. Like in adults, the similarity of genetic and epigenetic characteristics with other infiltrative high-grade gliomas suggests that pediatric GC does not represent a distinct molecular entity.


Children DNA methylation profiles Gliomatosis cerebri Molecular classification 



This work was supported by the United States National Institutes of Health Cancer Center Support (CORE) Grant P30 CA21765 and by the American Lebanese Syrian Associated Charities (ALSAC). We thank Geoffrey Neale and John Morris for assistance in performing the methylation studies. We thank Racquel Collins for her assistance in performing targeted sequencing.

Supplementary material

401_2015_1532_MOESM1_ESM.pdf (165 kb)
Supplemental Fig 1 Distribution of large areas of chromosomal gains or losses according to the methylation subgroup. Red and blue rectangles represent areas of chromosomal gains and losses, respectively. Abbreviation: MES, mesenchymal (PDF 164 kb)
401_2015_1532_MOESM2_ESM.pdf (902 kb)
Supplemental Fig 2 Overall survival of 30 pediatric patients with gliomatosis cerebri and histologically confirmed pure astrocytomas based on their tumor grade (PDF 901 kb)
401_2015_1532_MOESM3_ESM.pdf (898 kb)
Supplemental Fig 3 Overall survival of 32 pediatric patients with gliomatosis cerebri based on the presence of contrast enhancement (PDF 897 kb)
401_2015_1532_MOESM4_ESM.pdf (899 kb)
Supplemental Fig 4 Overall survival of type 1 vs. type 2 gliomatosis cerebri in 32 patients (PDF 898 kb)
401_2015_1532_MOESM5_ESM.pdf (900 kb)
Supplemental Fig 5 Overall survival of 18 pediatric patients with gliomatosis cerebri based on MGMT promoter methylation (PDF 900 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Alberto Broniscer
    • 1
    • 6
    Email author
  • Omar Chamdine
    • 1
  • Scott Hwang
    • 2
  • Tong Lin
    • 3
  • Stanley Pounds
    • 3
  • Arzu Onar-Thomas
    • 3
  • Sheila Shurtleff
    • 4
  • Sariah Allen
    • 4
  • Amar Gajjar
    • 1
    • 6
  • Paul Northcott
    • 5
  • Brent A. Orr
    • 4
  1. 1.Department of OncologySt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Department of Diagnostic ImagingSt. Jude Children’s Research HospitalMemphisUSA
  3. 3.Department of BiostatisticsSt. Jude Children’s Research HospitalMemphisUSA
  4. 4.Department of PathologySt. Jude Children’s Research HospitalMemphisUSA
  5. 5.Department of Developmental NeurobiologySt. Jude Children’s Research HospitalMemphisUSA
  6. 6.Department of PediatricsUniversity of Tennessee Health Science CenterMemphisUSA

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