Journal of Neuro-Oncology

, Volume 85, Issue 2, pp 111–122

FOXG1 dysregulation is a frequent event in medulloblastoma

  • Adekunle M. Adesina
  • Yummy Nguyen
  • Vidya Mehta
  • Hidehiro Takei
  • Patrick Stangeby
  • Sonya Crabtree
  • Murali Chintagumpala
  • Mary K. Gumerlock
Lab Investigation -human/animal tissue

DOI: 10.1007/s11060-007-9394-3

Cite this article as:
Adesina, A.M., Nguyen, Y., Mehta, V. et al. J Neurooncol (2007) 85: 111. doi:10.1007/s11060-007-9394-3

Abstract

Medulloblastomas represent 20% of malignant brain tumors of childhood. Although, they show multiple, non-random genomic alterations, no common, early genetic event involving all histologic types of medulloblastomas have been described. Nineteen medulloblastomas were analyzed using chromosomal comparative genomic hybridization (cCGH). Nine tumors with the most frequent number of genetic changes were further analyzed using bacterial artificial chromosome array CGH (aCGH). With aCGH, the frequency of gains and losses were higher than with cCGH. Chromosome 2p gains spanning 2p11–2p25 including N-myc locus, 2p24.1 were detected in 5/9 (55%) tumors while 14q12 gains were detected in 6/9 (67%) tumors. The 14q12 locus overlapped with the FOXGI gene locus. Quantitative real time PCR showed a 2–7-fold copy gain for FOXG1 in all the nine tumors. Protein expression was demonstrated by immunohistochemistry in all histologic types. The expression of FOXG1 and p21cip1 showed an inverse relationship. FOXG1 copy gain (>2 to 21 folds) was seen in 93% (55/59) of a validating set of tumors and showed a positive correlation with protein expression (Spearman’s rank order correlation coefficient = 0.276; P = 0.038) representing the first report of FOXG1 dysregulation in medulloblastoma. Modulation of FOXG1 expression in DAOY cell line using siRNA showed a modest decrease in proliferation with a 2-fold upregulation of p21cip1. Current reports indicate that FOXG1 represses TGF-β induced expression of p21cip1 and cytostasis, and forms a transcriptional repressor complex with Notch signaling induced hes1. Our findings are consistent with a role for FOXG1 in the inhibition of TGF-β induced cytostasis in medulloblastoma.

Keywords

Array comparative genomic hybridization FOXG1 medulloblastoma p21cip1 Pediatric brain tumors Primitive neuroectodermal tumor TGF-β signaling 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Adekunle M. Adesina
    • 1
  • Yummy Nguyen
    • 1
  • Vidya Mehta
    • 1
  • Hidehiro Takei
    • 1
  • Patrick Stangeby
    • 2
  • Sonya Crabtree
    • 2
  • Murali Chintagumpala
    • 3
  • Mary K. Gumerlock
    • 4
  1. 1.Department of Pathology, Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA
  2. 2.Department of PathologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  3. 3.Division of Hematology-Oncology, Texas Children’s Cancer CenterBaylor College of MedicineHoustonUSA
  4. 4.Department of NeurosurgeryUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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