Association between chromosome 1p and 19q loss and outcome in pediatric malignant gliomas: results from the CCG-945 cohort

Abstract

Background: Results of recent molecular studies on malignant gliomas in adults showed that deletions within the short arm of chromosome 1 and/or the long arm of chromosome 19 identified a prognostically favorable subgroup of tumors that often respond to conventional chemotherapy. To determine if this association applies to pediatric malignant gliomas, we examined the correlation between 1p and 19q deletions and outcome in the cohort derived from the Children's Cancer Group study 945, the largest randomized trial of such tumors completed to date.

Methods: Archival histopathologic material yielded tissue of sufficient quality and quantity for genotyping in 121 specimens. Sections were examined histologically and targets that contained malignant glioma were isolated by microdissection and subjected to polymerase-chain-reaction-based amplification of microsatellite loci using fluorochrome-labeled primers, followed by capillary electrophoresis, and fluorescent fragment analysis. One hundred and seven specimens had 2 alleles for at least 1 of the 3 1p loci examined, and were therefore informative for determining loss of heterozygosity, defined as at least a twofold difference in fluorescence intensity between the paired allelic bands; 99 were informative at 19q.

Results: Thirty-two tumors (29.9%) had loss of heterozygosity involving 1p, 27 (28%) involving 19q, and 13 involving both, an incidence consistent with previous reports involving adult malignant gliomas. However, outcome analyses of the entire cohort found no favorable association between 1p loss, 19q loss, or the combination, and survival. Subset analysis disclosed no association with outcome in either arm of the study (which compared efficacy of 2 chemotherapeutic regimens) or in subgroups stratified by age, tumor location, or tumor histology.

Conclusion: In contrast to recent observations of adult malignant gliomas, deletions involving chromosomes 1p or 19q did not predict a survival advantage in this series of pediatric high-grade gliomas, which might indicate that frequencies of various histologic and molecular subtypes of malignant gliomas differ between children and adults, and supports further efforts to identify prognostic indicators relevant to pediatric gliomas.