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Abstract: Glioblastoma multiforme (GBM), the most common malignant brain tumor of adults, is relatively rare in children. In a GBM affecting a 16-year-old boy, the tumor spread across the corpus callosum (butterfly glioma). This type of bilateral hemispheric growth has previously been thought to result from spread along the white matter tracts. Two samples obtained from opposite sides of the same tumor were analyzed comprehensively for loss of heterozygosity (LOH) and microsatellite instability (MSI). Amplification of EGFR and MDM2 was studied by means of multiplex polymerase chain reaction. Exons 5, 6, 7, and 8 of TP53 were screened for mutations by sequencing. In neither specimen were molecular alterations found in the EGFR, MDM2, or TP53 genes. The specimen obtained from the right hemisphere exhibited a high level of MSI and LOH in chromosome arms 5q, 9p, and 13q. The specimen from the left hemisphere exhibited LOH in chromosome arms 3p, 5q, 9p, 9q, 10p, 10q, and 13q. Here we propose four plausible hypothetical scenarios underlying the tumorigenesis of this GBM. [Copyright &y& Elsevier]

Abstract: We report here the mutational analysis of hSNF5/INI1 and TP53 genes performed on 11 specimens of choroid plexus carcinomas (CPC) in which a large number of abnormalities has been detected by molecular biology techniques. Loss of heterozygosity (LOH) analysis performed on six tumors revealed losses on chromosomes 1, 3, 5, 9, 10, 13, 16, 18, and 22. However, there were no abnormalities on 17p and mutations of the TP53 gene have been observed for two tumors comprising exons 5 and 7, respectively. Exon 4 of hSNF5/INI1 was mutated in one tumor with LOH restricted to the hSNF5/INI1 locus. There was no coexistence of mutations in both analyzed genes. Our analysis confirms the presence of the hSNF5/INI1 mutations and proves involvement of TP53 mutations in sporadic cases of CPC. [Copyright &y& Elsevier]

The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness. Methods Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB. Results There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p < 0.001), while TTF-1 correlated negatively with the age of patients (p = 0.039). PAX5 expression correlated with ISL-1 (p = 0.039) and showed a trend toward higher expression in the desmoplastic subtype (p = 0.069). Conclusions SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients. [ABSTRACT FROM AUTHOR]

Abstract: Pleomorphic xanthoastrocytoma (PXA) is a tumor of astrocytic lineage that may have anaplastic features; such a phenotype usually correlates with a less favorable outcome. The molecular profile of PXA differs from other astrocytic tumors, but the molecular mechanisms of its formation and progression are still undefined. We analyzed a loss of heterozygosity and mutations of the SMARCB1 (also known as SNF5 or INI1) and TP53 genes in four cases of PXA. In just one case a TP53 mutation (Cys238Tyr) was readily detectable at the mRNA level, but it was almost undetectable during DNA sequencing. This case was also the only one exhibiting anaplastic features and TP53 overexpression as defined by immunohistochemistry. This observation supports our earlier findings on discrepancies in TP53 status in glioblastomas. We suggest that the incidence of TP53 mutations in pleomorphic xanthoastrocytoma may be underestimated and that molecular approaches should be used for greater diagnostic precision. [Copyright &y& Elsevier]

Abstract: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and the most frequent associated genetic alteration is loss of heterozygosity on chromosome region 7p13. Two genes mapping to this region, KCTD11 (alias REN) and HIC1, have been proposed as involved in MB pathogenesis. We used real-time polymerase chain reaction in 20 tissue samples of primary MB to examine the transcriptional level of the two genes, with reference to two types of controls: adult cerebellum and fetal neural stem cells. A significant reduction of KCTD11 expression relative to adult normal cerebellum was detected in 14 of 20 (70%) of MB samples. Neural stem cells had even lower levels of KCTD11 expression than did MB. HIC1 gene expression was low (∼100 times lower than KCTD11 expression) in MB, and low also in both adult cerebellum and neural stem cells. Hypermethylation of the 5′UTR or the central region of HIC1 (or both) was detected in a significant number of MB samples, as well as in cerebellum and neural stem cells. Our data suggest that KCTD11 may play an important role in MB tumorigenesis, but do not support the role of HIC1 in this tumor development. We argue that recognition of the gene or genes important in MB tumorigenesis depends in part on defining an appropriate control. [Copyright &y& Elsevier]