RESUMO
The molecular pathogenesis of pleomorphic xanthoastrocytoma (PXA), a rare astrocytic brain tumor with a 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% of tumors. Other recurrent losses affected chromosomes 17 (10%), 8, 18, 22 (4% each). Recurrent gains were identified on chromosomes X (16%), 7, 9q, 20 (8% each), 4, 5, 19 (4% each). Two tumors demonstrated amplifications mapping to 2p23-p25, 4p15, 12q13, 12q21, 21q21 and 21q22. Analysis of 10 PXAs with available high molecular weight DNA by high-resolution array-based CGH indicated homozygous 9p21.3 deletions involving the CDKN2A/p14(ARF)/CDKN2B loci in six tumors (60%). Interphase fluorescence in situ hybridization to tissue sections confirmed the presence of tumor cells with homozygous 9p21.3 deletions. Mutational analysis of candidate genes on 9q, PTCH and TSC1, revealed no mutations in PXAs with 9q loss and no evidence of TSC1 promoter methylation. However, PXAs consistently showed low TSC1 transcript levels. Taken together, our study identifies loss of chromosome 9 as the most common chromosomal imbalance in PXAs and suggests important roles for homozygous CDKN2A/p14(ARF)/CDKN2B deletion as well as low TSC1 mRNA expression in these tumors.
Assuntos
Astrocitoma/genética , Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Deleção de Genes , Proteína Supressora de Tumor p14ARF/genética , Proteínas Supressoras de Tumor/deficiência , Adolescente , Adulto , Criança , Pré-Escolar , Inibidor de Quinase Dependente de Ciclina p15/deficiência , Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Feminino , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , Proteína 1 do Complexo Esclerose Tuberosa , Proteína Supressora de Tumor p14ARF/deficiência , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/genéticaRESUMO
A report is given on the detection of verotoxin-producing E. coli (VTEC) strains from field isolates of healthy or ill cattle (n = 141), pigs (n = 306), sheep (n = 15), cats (n = 29) and dogs (n = 25) in the region of the new federal land Sachsen-Anhalt. 5% of the strains isolated from cattle, 32% from pigs, 20% from sheep, 4% from dogs and 0% from cats have shown VTEC. The E. coli-strains were checked for the presence of other factors of virulence, too. A good correlation (82%) was found between the colonization factor F107 and SLT 2/2v-containing strains from pigs in the region of Sachsen-Anhalt, too. Enterohemolysin was not found in SLT 2/2v-positive strains. 91% of the VTEC, isolated from pigs, produced alpha-Hemolysin. The correlation of SLT-containing strains and the production of enterohemolysin was confirmed for ruminants, only. Plasmidprofilings of VTEC from pigs showed mainly a 60 MDa or a 68 MDa plasmid or both, too. The occurrence of heat labile (LT) and in some cases of heat stable (ST) toxin was also checked, to differentiate the VTEC-strains from the enterotoxigenic E. coli strains (ETEC). These investigations showed, that VTEC produce SLT almost without exception. Correlations and conclusions on the pathogenicity for humans are discussed.
