mRNA and miRNA Expression Analyses of the MYC/E2F/miR-17-92 Network in the Most Common Pediatric Brain Tumors.

Numerous molecular factors disrupt the correctness of the cell cycle process leading to the development of cancer due to increased cell proliferation. Among known causative factors of such process is abnormal gene expression. Nowadays in the light of current knowledge such alterations are frequently considered in the context of mRNA-miRNA correlation. One of the molecular factors with potential value in tumorigenesis is the feedback loop between MYC and E2F genes in which miR-17-5p and miR-20a from the miR-17-92 cluster are involved. The current literature shows that overexpression of the members of the OncomiR-1 are involved in the development of many solid tumors. In the present work, we investigated the expression of components of the MYC/E2F/miR-17-92 network and their closely related elements including members of MYC and E2F families and miRNAs from two paralogs of miR-17-92: miR-106b-25 and miR-106a-363, in the most common brain tumors of childhood, pilocytic astrocytoma (PA), WHO grade 1; ependymoma (EP), WHO grade 2; and medulloblastoma (MB), WHO grade 4. We showed that the highest gene expression was observed in the MYC family for MYCN and in the E2F family for E2F2. Positive correlation was observed between the gene expression and tumor grade and type, with the highest expression being noted for medulloblastomas, followed by ependymomas, and the lowest for pilocytic astrocytomas. Most members of miR-17-92, miR-106a-363 and miR-106b-25 clusters were upregulated and the highest expression was noted for miR-18a and miR-18b. The rest of the miRNAs, including miR-19a, miR-92a, miR-106a, miR-93, or miR-25 also showed high values. miR-17-5p, miR-20a obtained a high level of expression in medulloblastomas and ependymomas, while close to the control in the pilocytic astrocytoma samples. miRNA expression also depended on tumor grade and histology.

GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis.

Deletions of 1p occur in approximately 30% of meningiomas. Based on loss of heterozygosity (LOH) analysis, two regions on 1p have been suspected to be carriers of tumor suppressor genes. We chose the GADD45A and EPB41 genes as tumor suppressor candidates based on their function and chromosomal localization. We analyzed 19 cases of meningioma with LOH of 1p by means of sequencing of the GADD45A gene and Western blotting of the GADD45a protein. Twenty cases of meningioma without 1p LOH were also analyzed by Western blotting to find out if changes of the GADD45a protein expression occurred. Nineteen samples with 1p LOH (12 grade I; 7 grade II, WHO classification) and 20 samples without 1p LOH (18 grade I; 2 grade II) were also analyzed by means of real-time polymerase chain reaction to find abnormalities in EPB41 mRNA levels in meningioma. LOH analysis was performed using seven microsatellite markers: D1S508 (1p36.2), D1S199 (1p36.1) D1S2734 (1p36.1), D1S2720 (1p34), D1S197 (1p32), D1S162 (1p32), D1S429 (1p11). LOH analysis confirmed previously described localization of putative tumor suppressor genes on 1p and involvement in meningioma pathogenesis (1p36 and 1p32). The open reading frame of GADD45A and intron splicing sites showed neither mutations nor polymorphisms. GADD45a protein molecular weight and expression level were unaltered in meningiomas with and without 1p LOH. We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. EPB41 gene expression was unchanged in all analyzed meningiomas. This suggests that involvement of the EPB41 gene (4.1R protein) in meningioma pathogenesis should be reconsidered.

Atypical molecular background of glioblastoma and meningioma developed in a patient with Li-Fraumeni syndrome.

We observed three neoplasms with completely different histologies: malignant fibrous histiocytoma (MFH), atypical meningioma (AM), and glioblastoma (GB), developing in a patient with Li-Fraumeni syndrome. By using a combined molecular approach we performed molecular characterization of all three tumours. Data obtained showed an interesting molecular background of the AM and GB. AM showed TP53mutations and a 22q loss of heterozygosity (LOH). GB showed epidermal growth factor receptor (EGFR) amplification and TP53 mutations, whereas P16, PTEN, Rbwere intact in terms of LOH and/or multiplex PCR (polymerase chain reaction) analysis. Additionally, GB has a 1q LOH, which is an extremely rare alteration in glioblastomas. Identical 1q LOH was also observed in MFH.

Amyloid-beta and tau proteins as biochemical markers of Alzheimer's disease.

With the development of new therapeutic strategies, and the concept of mild cognitive impairment (MCI) as an early stage of Alzheimer's disease (AD), there is an increasing need for an early and accurate diagnosis of sporadic AD. Therefore, biological markers allowing a positive diagnosis early in the course of the disease are highly desirable. The most extensively evaluated markers of sporadic AD are amyloid-beta proteins and levels of both total and phosphorylated microtubule-associated protein tau. In this study, we review the currently available data on the aforementioned markers assessed in the cerebrospinal fluid or plasma, alone and in combinations, focusing on their clinical applicability including sensitivity in the diagnosis of AD and mild cognitive impairment, specificity in discriminating AD from other dementias and correlations with the disease progression and apolipoprotein E genotype. We also analyze advantages and potential drawbacks of using biomarkers in the laboratory diagnosis of AD.