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Alterations of DNA copy number are believed to be important indicators of tumor progression in human astrocytoma. We used an array of bacterial artificial chromosomes to map relative DNA copy number in 50 primary glioblastoma multiforme tumors at f1.4-Mb resolution.We identified 33 candidate sites for amplification and homozygous deletion in these tumors.We identified three major genetic subgroups within these glioblastoma multiforme tumors: tumors with chromosome 7 gain and chromosome10 loss, tumors with only chromosome 10 loss in the absence of chromosome 7 gain, and tumors without copy number change in chromosomes 7 or 10. The significance of these genetic groups to therapeutics needs further study.Studies suggest that astrocytic brain tumor behavior is related to genetic defects acquired over the course of tumor development (1 -6). It is believed that understanding these genetic defects will help predict response to treatment and patient outcome. Previous studies using comparative genomic hybridization (CGH; refs. 7, 8) related radiation sensitivity of tumors and patients' survival to copy number aberrations (CNA) on several chromosomes (2, 3). This report describes CNAs identified on a bacterial artificial chromosome (BAC) array of f1.4-Mb resolution [array comparative genomic hybridization (aCGH)], in a set of 50 glioblastoma multiforme (GBM).We compared specificity and sensitivity of the chromosome CGH and aCGH techniques by comparing array and chromosome CGH in the same tumor samples, by counting fluorescence in situ hybridization (FISH) signals generated by BAC clones used in the array, and by using real-time quantitative PCR. The results obtained by aCGH confirmed other characterizations of the GBM genome.Analysis of high-resolution aCGH data identified genetic subgroups in this set of GBM and loci for candidate oncogenes and tumor suppressor genes, many of which were previously unknown. We expect that future higher resolution studies of these regions will lead to identification of target genes for therapy. Materials and MethodsCell lines. The cell lines used in this study (SF767, SF126, U343MG, and SF210) were obtained from the Tissue Bank at the Brain Tumor Research Center, University of California, San Francisco (UCSF; ref. 9). Cells were cultured in minimal essential medium with Earle's buffered salt solution supplemented with 10% FCS and nonessential amino acids.Tumor DNA. Fifty tumor samples (GBM, grade 4 astrocytoma) were obtained from the tissue bank at the Brain Tumor Research Center, UCSF. All patients signed consent for specimens to be used for research purposes. The samples were originally chosen for evaluation using chromosome CGH (8). Tumor specimens were snap-frozen in liquid nitrogen immediately after resection and stored at À80jC. Tumors were diagnosed by the Division of Neuropathology at UCSF according to WHO classification (10). Sections on both sides contiguous to the processed specimens were histologically assessed to determine the percentage of tumor cells present in the ...

Medulloblastomas are genetically heterogeneous and can be categorized into separate genetic subgroups by their CNAs using unsupervised cluster analysis and SAM. i(17)(q10) was a significant independent negative prognostic factor. Infant medulloblastomas may be a distinct genetic subset from those of older patients.

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