Genetic Predictors of Unfavorable Outcomes in Pediatric Medulloblastoma
Patricia A. Stoeck
Howard J. Weinstein
Outcome Prediction in Pediatric Medulloblastoma Based on DNA Copy-Number Aberrations of Chromosomes 6q and 17q and the MYC and MYCN Loci
Pfister S, Remke M, Benner A, et al. J Clin Oncol. 2009;27(10):1627–1636
Background
Medulloblastoma is the most common pediatric brain tumor. Although 60% of these patients are ultimately cured, 10% to 15% die within 2 years of diagnosis and those who survive face significant adverse treatment effects. Previously, age, metastatic disease, and scope of surgical resection determined stratification into standard or high-risk grouping, but significant heterogeneity in outcomes was observed within groups. This study sought to identify chromosomal regions predictive of disease outcome to refine conventional staging methods.
Objectives
To incorporate specific genetic aberrations into a model for determining prognosis, including overall survival (OS) and progression-free survival (PFS), in pediatric medulloblastoma.
Methods
Screening/validation study with screening tissue samples from Germany and Russia collected from 1994 to 2002 and validation samples from Russia collected from 1995 to 2006.
Patients
80 screening samples and 260 validation samples from children with medulloblastoma. All patients received standard therapy per German protocols.
Intervention
Comparative genomic hybridization microarray was performed on screening samples to identify chromosomal loci of interest. Fluorescence in situ hybridization was used for validation samples looking for these loci: chromosome 6q (loss and gain), 17q (gain and isochromosome i[17q]), and MYC/MYCN amplification.
Outcomes
Primary outcome was the prognostic significance of these genetic variations on OS and PFS. Secondary outcomes were classification of cytogenetic risk groups and hazard ratios for each group.
