Genetic alterations in pediatric high-grade astrocytomas

High-grade astrocytomas are tumors that are uncommon in children. Relativel y few studies have been performed on their molecular properties and so it i s not certain whether they follow different genetic pathways from those des cribed in adult diffuse astrocytomas. In this study we evaluated 24 pediatr ic high-grade astrocytomas (11 anaplastic astrocytomas and 13 glioblastomas ) all of which were sporadic and primary. We studied mutations of p53, phos phatase and tensin homolog (PTEN), loss of heterozygosity (LOH) of chromoso mes 17p13, 9p21 and 10q23-25, amplification of epidermal growth factor rece ptor (EGFR), and overexpression of EGFR and p53 protein In addition, we sea rched for microsatellite instability (MSI) by using MSI sensitive and speci fic microsatellite markers. p53 mutations were found in 38% (9/24) of the h igh-grade astrocytomas and all brain stem tumors except 2 (71%, 5/7) had p5 3 mutations. PTEN mutations were found in 8% (P2/24) of high-grade astrocyt omas. However, no EGFR amplification was found in anp of them. LOH was foun d at 17p13.1 in 50% (3/6 informative tumors), 9p21 in 83% (5/6 informative tumors), and 10q23-25 in 78% (7/9 informative tumors). Four tumors showed M SI, and 2 of them that showed widespread MSI were regarded as tumors with r eplication error (RER+) phenotype. All 4 tumors with MSI showed concurrent LOH of 9p21 and 10q23-25. Combining gene alterations, LOH, MSI, and gene mu tations, inactivation of both alleles of PTEN and p53 was found in 57% (4/7 informative tumors) and 50% (3/6 informative tumors) of the cases respecti vely: We conclude that development of pediatric high-grade astrocytomas may follow pathways different from the primary or secondary paradigm of adult glioblastomas. In a subset of these tumors, genomic instability tvas also i mplicated. Copyright (C) 1999 by W.B. Saunders Company.