Frequent loss of chromosome 9, homozygous CDKN2A/p14ARF/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas

摘要: The molecular pathogenesis of pleomorphic xanthoastrocytoma (PXA), a rare astrocytic brain tumor with relatively favorable prognosis, is still poorly understood. We characterized 50 PXAs by comparative genomic hybridization (CGH) and found the most common imbalance to be loss on chromosome 9 in 50% tumors. Other recurrent losses affected chromosomes 17 (10%), 8, 18, 22 (4% each). Recurrent gains were identified X (16%), 7, 9q, 20 (8% each), 4, 5, 19 Two tumors demonstrated amplifications mapping 2p23-p25, 4p15, 12q13, 12q21, 21q21 21q22. Analysis 10 available high weight DNA high-resolution array-based CGH indicated homozygous 9p21.3 deletions involving CDKN2A/p14(ARF)/CDKN2B loci six (60%). Interphase fluorescence situ tissue sections confirmed presence cells deletions. Mutational analysis candidate genes PTCH TSC1, revealed no mutations 9q evidence TSC1 promoter methylation. However, consistently showed low transcript levels. Taken together, our study identifies as chromosomal suggests important roles for deletion well mRNA expression these