H Ohgaki

..004), suggesting a slightly higher susceptibility to gastric carcinogenesis induced by MNU in p53(+/-) mice. Mol. Carcinog. 28:97-101, 2000...

..0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms...

..G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas, suggesting that the acquisition of TP53 mutations in these glioblastoma subtypes may occur through different mechanisms...

..These results suggest that some histologic features in glioblastomas are associated with specific genetic alterations and with clinical outcome...

..8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma...

..Despite a similar histologic appearance, primary and secondary glioblastomas are distinct tumor entities that originate from different precursor cells and may require different therapeutic approaches...

..In this study, we investigated whether BCCIP is altered in astrocytomas...

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..These results suggest that disruption of the Wnt pathway through APC mutations is infrequent, but may be involved in the pathogenesis of a small subset of human lung carcinomas...

..In this review, we summarize the current status of genetic alterations and signaling pathways operative in the evolution of astrocytic and oligodendroglial tumors...

..In this review, we provide a brief overview of these syndromes...

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..This has significant implications, particularly for the development of novel, targeted therapies, as discussed in this review...

..These results suggest that mutations in these mitotic spindle checkpoint genes do not play a significant role in the causation of chromosomal instability in glioblastomas...

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..These results indicate that promoter hypermethylation is a late event during astrocytoma progression and is the major mechanism underlying loss of RB1 expression in glioblastomas...

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..By comparison, the levels of the Balpha and Calpha subunits were mostly normal. Our data indicate that these tumors contain very low levels of core and holoenzyme and high amounts of unregulated catalytic C subunit...

..Multivariate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors...

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..The presence in these neoplasms of multiple mutations in tumor suppressor genes suggests the involvement of a novel disease mechanism but there was no indication of a DNA mismatch repair deficiency or of an inherited tumor syndrome...

..Thus, simultaneous disruption of the RB1/CDK4/p16INK4a/p15INK4b and the TP53/p14ARF/MDM2 pathways occurs in 45% (9/20) of anaplastic oligodendrogliomas, suggesting that these phenomena contribute to their malignant phenotype...

..Although germline APC mutations are a well established cause of familial colon and brain tumors (Turcot syndrome), this study provides the first evidence that APC mutations are also operative in a subset of sporadic medulloblastomas...

..These results suggest that multiple TP53 mutations in glioblastomas are due to deficient repair of DNA double-strand breaks caused by mutational inactivation of the NBS1 gene...

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..07-1.71). Detailed analyses revealed that TP53 codon 72 Pro allele was significantly associated with shorter survival among patients with glioblastomas carrying a TP53 mutation, and among those treated with surgery plus radiotherapy...

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..These data are in line with previous studies showing that brain tissues are more susceptible to oxidative stress and lipid peroxidation than other tissues...

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..e., chronic liver injury and cirrhosis, but tumors associated with alcoholism had more frequent alterations in the RB1 and p53 pathways than those caused by HCV infection...

..This is the first observation indicating that inherited SDHD mutations may occasionally cause the development of paragangliomas in the central nervous system...

..In all cases, identical TP53 mutations were identified in both cell types, indicating that gemistocytes are indeed neoplastic cells. Their lack of proliferative activity may indicate terminal differentiation...

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..These PARP-1/p53 double null mice represent a novel model for the pathogenesis of human medulloblastomas...

..There was no correlation with LOH on chromosomes 1p/19q, suggesting that MGMT may not be a prognostic marker for oligodendrogliomas...

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..This remarkably selective occurrence of R132C mutations may reflect differences in the sequence of genetic events, with a preference for R132C mutations in astrocytes or precursor cells that already carry a germline TP53 mutation...

..Analysis of a polymorphic site in exon 2 further showed that p73 was mono-allelically expressed in 6 out of 7 primary gliomas with heterozygous GC/TA polymorphism...

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..70; 95% CI 0.48-1.01). These results suggest that MGMT methylation may be associated with susceptibility to acquire TP53 G:C-->A:T mutations, and that MGMT polymorphisms may affect the risk and prognosis of glioblastomas...

..These results suggest that the EGFR/PTEN/PI3K pathway is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas...

..Such implant-induced sarcoma development in Trp53+/- mice could be useful for studying molecular mechanisms and developing new strategies for chemoprevention in human carcinogenesis induced by chronic inflammation and/or foreign bodies...

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..004). These observations have clinical implications for genetic testing and tumor surveillance in LFS/LFL families...

..Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different...

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..There may be functional interactions between NBS1 and the TP53 pathways. The objective of the present study is to assess whether NBS1 mutations play a role in the pathogenesis of sporadic medulloblastomas...

..Since there are multiple complementary, inverted sequences present in the AXIN1 gene, these large deletions may represent RT-PCR errors due to stem-loop secondary structures...

..Glands of Gleason pattern 3 are genetically heterogeneous, some containing the same genetic alterations observed in glands of Gleason pattern 4...

..While iNOS may have protective effects against nonthymic lymphomagenesis, the regulation of cytokine production by iNOS may be involved in the underlying mechanism of antilymphomagenesis effects in the peripheral lymphoid organ...

..0001). These results suggest that genetic analyses are possible using WGA-DNA extracted from paraffin sections, but that they should be performed with a carefully optimized and controlled protocol...

..048). These results demonstrate that oligodendrogliomas and low-grade astrocytomas differ in their gene expression profiles, and that there are subgroups of oligodendroglioma with distinct expression profiles related to clinical outcome...

..Instead, it appears that granular cell change occurs across genetic subsets. The high frequency of allelic loss, especially on 9p and 10q, may confer aggressive growth potential and be related to their rapid clinical progression...

..These findings indicate that degree of anaplasia is the most significant histologic feature predictive of the survival of medulloblastoma patients...

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..Thus, induction of B-cell and T-cell apoptosis via interactions of CD70 expressed on glioma cells and CD27 expressed on B and T cells may be a novel way for the immune escape of malignant gliomas...

..Nonetheless, the strong nuclear expression of p53 in these and other pediatric GBMs could indicate that p53 dysregulation is important to tumorigenesis...