Supratentorial primitive neuroectodermal tumors (stPNETs) and medulloblastomas have long been thought to arise from a common cell type in the subventricular germinal matrix. Because of the infrequent occurrence of stPNETs, little is known about their genetic background. Here, we performed a genome-wide screening for DNA copy-number aberrations in 10 supratentorial PNETs using array-based comparative genomic hybridization (array-CGH). Comparing our findings with data from a previous array-CGH study on 47 medulloblastomas, we identified differences in the frequency of copy-number losses at chromosome regions 1p12-22.1 and 9p, and gains at 19p, all of them more frequently occurring in stPNETs. In contrast to previous reports, we detected chromosome 17 aberrations by array-CGH in 2/10 stPNETs. To validate our findings obtained by array-CGH, we analyzed the loci of interest by fluorescence in situ hybridization in an independent set of 11 stPNETs and found deletions of 9p21 in 5/11 tumors of the second set, three of them being homozygous. All 9p21 deletions were associated with loss of CDKN2A protein expression. Altogether, CDKN2A deletions were detected in 7/21 stPNETs including four homozygous deletions, whereas such deletions were only found in 4/112 medulloblastomas, all of these being heterozygous (P < 0.001). Gains of 19p (14% vs. 0% in medulloblastomas, P = 0.02) were found to be significantly more frequent in stPNETs, whereas gains of 17q (14% vs. 45% in medulloblastomas, P = 0.02) were confirmed to be more frequent in medulloblastomas. These data further support the hypothesis of two different tumor entities of embryonal neuroepithelial tumors with characteristic genetic aberrations. (c) 2007 Wiley-Liss, Inc.
