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"Large cell/anaplastic" medulloblastomas: a Pediatric Oncology Group Study
H G Brown1, J L Kepner, E J Perlman
1Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Journal of Neuropathology and Experimental Neurology
|November 18, 2000
Summary
Large cell and anaplastic medulloblastomas (LC/A MBs) are rare variants, accounting for 4% of cases. These aggressive tumors are linked to genetic amplifications and exhibit significantly poorer survival rates.
Area of Science:
- Pediatric Oncology
- Molecular Genetics
- Cancer Biology
Background:
- Medulloblastomas (MBs) are the most common malignant brain tumors in children.
- Histopathological variants, such as large cell (LC) and anaplastic (A) MBs, are associated with distinct clinical outcomes.
- Understanding the genetic underpinnings of these aggressive variants is crucial for improving prognostication and treatment.
Purpose of the Study:
- To determine the incidence and prognostic significance of "large cell" and "anaplastic" medulloblastoma variants.
- To investigate the association between the LC/A MB phenotype and specific genetic alterations, including c-myc and n-myc amplification.
- To correlate histological findings with cytogenetic data and patient survival.
Main Methods:
- Retrospective review of 495 medulloblastomas from Pediatric Oncology Group (POG) protocols.
- Histopathological assessment to identify "large cell" and "anaplastic" features.
- Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) to detect gene amplifications (c-myc, n-myc) and chromosomal abnormalities (isochromosome 17q, monosomy 22).
- Kaplan-Meier survival analysis and logrank testing to compare survival probabilities between LC/A MB and control groups.
Main Results:
- Twenty-one cases (approximately 4%) were classified as combined LC/A medulloblastomas.
- The LC/A MB group exhibited significantly poorer survival compared to controls (p < 0.0001).
- c-myc amplification was detected in 4 of 11 LC/A cases by FISH, with additional cases showing high-level gain at 8q24 (CGH) or n-myc amplification at 2p13.
- Isochromosome 17q was identified in 3 of 4 successfully studied LC/A cases via CGH.
- Monosomy 22 was notably absent in LC/A MBs.
Conclusions:
- The LC/A MB phenotype is associated with a significantly worse prognosis.
- Genetic alterations, particularly c-myc and possibly n-myc amplification, may contribute to the LC/A MB phenotype.
- These findings reinforce the link between specific cytogenetic abnormalities and aggressive medulloblastoma subtypes.