Clinical and molecular characteristics of congenital glioblastoma

Margaret E. MacY, Diane K. Birks, Valerie N. Barton, Michael H. Chan, Andrew M. Donson, B. K. Kleinschmidt-Demasters, Lynne T. Bemis, Michael H. Handler, Nicholas K. Foreman

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Congenital glioblastoma (cGBM) is an uncommon tumor of infancy with a reported variable but often poor cure rate, even with intensive therapy. Five patients with cGBMs, arising de novo and not in familial tumor predisposition kindreds, were studied for histological and biological features, using Affymetrix microarray. Tumors were large, often associated with hemorrhage, extended into the thalamus, and often bulged into the ventricles. One patient died acutely from bleeding at the time of operation. The 4 surviving patients underwent surgery (1 gross total resection, 3 subtotal resections or biopsies) and moderate intensity chemotherapy without radiation, and remain progression-free at a median time of 36 months (range, 30110 months). Affymetrix microarrays measured gene expression on the 3 cGBMs from which frozen tissue was available. Unsupervised hierarchical clustering of cGBMs versus 168 other central nervous system tumors demonstrated that cGBMs clustered most closely with other high-grade gliomas. Gene expression profiles of cGBMs were compared with non-congenital pediatric and adult GBMs. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only 31 differentially expressed genes identified (false discovery rate, <0.05). Unique molecular features of cGBMs included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia. cGBMs show histological and biological overlap with pediatric and adult GBMs but appear to have a more favorable outcome, with good response to moderate intensity chemotherapy with only subtotal resection or biopsy. Further study may determine whether identified gene expression differences contribute to the improved survival seen in these tumors.

Original languageEnglish (US)
Pages (from-to)931-941
Number of pages11
JournalNeuro-Oncology
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2012

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Glioblastoma
Pediatrics
Gene Expression
Neoplasms
Biopsy
Drug Therapy
Central Nervous System Neoplasms
Bleeding Time
Thalamus
Transcriptome
Glioma
Cluster Analysis
Radiation
Hemorrhage
Glucose
Survival
Genes
Therapeutics

Keywords

  • brain tumor
  • gene expression
  • glioblastoma
  • infant
  • microarray

Cite this

MacY, M. E., Birks, D. K., Barton, V. N., Chan, M. H., Donson, A. M., Kleinschmidt-Demasters, B. K., ... Foreman, N. K. (2012). Clinical and molecular characteristics of congenital glioblastoma. Neuro-Oncology, 14(7), 931-941. https://doi.org/10.1093/neuonc/nos125

Clinical and molecular characteristics of congenital glioblastoma. / MacY, Margaret E.; Birks, Diane K.; Barton, Valerie N.; Chan, Michael H.; Donson, Andrew M.; Kleinschmidt-Demasters, B. K.; Bemis, Lynne T.; Handler, Michael H.; Foreman, Nicholas K.

In: Neuro-Oncology, Vol. 14, No. 7, 01.07.2012, p. 931-941.

Research output: Contribution to journalArticle

MacY, ME, Birks, DK, Barton, VN, Chan, MH, Donson, AM, Kleinschmidt-Demasters, BK, Bemis, LT, Handler, MH & Foreman, NK 2012, 'Clinical and molecular characteristics of congenital glioblastoma', Neuro-Oncology, vol. 14, no. 7, pp. 931-941. https://doi.org/10.1093/neuonc/nos125
MacY ME, Birks DK, Barton VN, Chan MH, Donson AM, Kleinschmidt-Demasters BK et al. Clinical and molecular characteristics of congenital glioblastoma. Neuro-Oncology. 2012 Jul 1;14(7):931-941. https://doi.org/10.1093/neuonc/nos125
MacY, Margaret E. ; Birks, Diane K. ; Barton, Valerie N. ; Chan, Michael H. ; Donson, Andrew M. ; Kleinschmidt-Demasters, B. K. ; Bemis, Lynne T. ; Handler, Michael H. ; Foreman, Nicholas K. / Clinical and molecular characteristics of congenital glioblastoma. In: Neuro-Oncology. 2012 ; Vol. 14, No. 7. pp. 931-941.
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