Genome Wide Copy Number Abnormalities in Pediatric Medulloblastomas as Assessed by Array Comparative Genome Hybridization

Array-based comparative genomic hybridization was used to characterize 22 medulloblastomas in order to precisely define genetic alterations in these malignant childhood brain tumors. The 17p(-)/17q(+) copy number abnormality (CNA), consistent with the formation of isochromosome 17q, was the most common event (8/22). Amplifications in this series included MYCL, MYCN and MYC previously implicated in medulloblastoma pathogenesis, as well as novel amplicons on chromosomes 2, 4, 11 and 12. Losses involving chromosomes 1, 2, 8, 10, 11, 16 and 19 and gains of chromosomes 4, 7, 8, 9 and 18 were seen in greater than 20% of tumors in this series. A homozygous deletion in 11p15 defines the minimal region of loss on this chromosome arm. In order to map the minimal regions involved in losses, gains and amplifications, we combined aCGH data from this series with that of two others obtained using the same RPCI BAC arrays. As a result of this combined analysis of 72 samples, we have defined specific regions on chromosomes 1, 8p, 10q, 11p and 16q which are frequently involved in CNAs in medulloblastomas. Using high density oligonucleotide expression arrays, candidate genes were identified within these consistently involved regions in a subset of the tumors.