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Updated: Jul 14, 2026
Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice
Published on: October 3, 2010
FOXG1 dysregulation is a frequent event in medulloblastoma
Adekunle M Adesina1, Yummy Nguyen, Vidya Mehta
1Department of Pathology, Texas Children's Cancer Center, Baylor College of Medicine, One Baylor Plaza, Rm. 286A, Houston, TX 77030, USA. aadesina@bcm.tmc.edu
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-beta 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-beta induced cytostasis in medulloblastoma.
Insights
This study identifies FOXG1 gene copy gain as a common early event in medulloblastoma, a pediatric brain tumor. This dysregulation correlates with protein expression and may inhibit tumor cell growth inhibition.
Area of Science:
- Pediatric oncology
- Cancer genomics
- Molecular biology
Background:
- Medulloblastomas are common pediatric malignant brain tumors with known genomic alterations.
- No consistent early genetic event has been identified across all medulloblastoma subtypes.
Purpose of the Study:
- To investigate common early genetic events in medulloblastoma.
- To identify novel genetic alterations and their role in medulloblastoma pathogenesis.
Main Methods:
- Comparative genomic hybridization (cCGH) and array CGH (aCGH) were used to analyze genomic alterations in 19 medulloblastomas.
- Quantitative real-time PCR and immunohistochemistry assessed FOXG1 gene copy number and protein expression.
- siRNA-mediated knockdown of FOXG1 in DAOY cell line evaluated functional impact.
Main Results:
- Array CGH revealed higher frequencies of gains and losses compared to cCGH.
- Gains in chromosome 2p (including N-myc locus) and 14q12 (overlapping FOXG1 locus) were frequent.
- FOXG1 copy gain was detected in 55% of tumors analyzed by aCGH and in 93% of a larger validation set, correlating positively with protein expression.
Conclusions:
- FOXG1 dysregulation, specifically copy gain, represents a common early genetic event in medulloblastoma.
- FOXG1 copy gain is associated with increased protein expression and may contribute to medulloblastoma development by inhibiting TGF-beta-induced cytostasis.
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