Transcription profiling of human glial brain tumors
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ABSTRACT: Gene expression profiling in 50 glial brain tumors and 4 normal brains using 42,000-feature cDNA microarrays (from total RNA). Tumors: 50 fresh-frozen glioma specimens subjected to standard WHO classification. Specimens included astrocytic [2 juvenile pilocytic astrocytomas, 1 low-grade astrocytic glioma, 1 anaplastic astrocytomas, 31 glioblastomas (of these 2 secondary glioblastomas and 2 gliosarcomas)], oligodendroglial [5 oligodendrogliomas, 3 anaplastic oligodendrogliomas], and 6 anaplastic oligoastrocytomas tumors. One tumor had been classified as glioneuronal neoplasm. Normal brain was purchased from Stratagene. Stratagene Universal Common Reference was used as reference RNA. The results provide insights into molecular mechanisms and pathways associated with gliomagenesis.
Project description:Gene expression profiling in 50 glial brain tumors and 4 normal brains using 42,000-feature cDNA microarrays (from total RNA). Tumors: 50 fresh-frozen glioma specimens subjected to standard WHO classification. Specimens included astrocytic [2 juvenile pilocytic astrocytomas, 1 low-grade astrocytic glioma, 1 anaplastic astrocytomas, 31 glioblastomas (of these 2 secondary glioblastomas and 2 gliosarcomas)], oligodendroglial [5 oligodendrogliomas, 3 anaplastic oligodendrogliomas], and 6 anaplastic oligoastrocytomas tumors. One tumor had been classified as glioneuronal neoplasm. Normal brain was purchased from Stratagene. Stratagene Universal Common Reference was used as reference RNA. The results provide insights into molecular mechanisms and pathways associated with gliomagenesis.
Project description:Gene expression profiling in 50 glial brain tumors and 4 normal brains using 42,000-feature cDNA microarrays (from total RNA). Tumors: 50 fresh-frozen glioma specimens subjected to standard WHO classification. Specimens included astrocytic [2 juvenile pilocytic astrocytomas, 1 low-grade astrocytic glioma, 1 anaplastic astrocytomas, 31 glioblastomas (of these 2 secondary glioblastomas and 2 gliosarcomas)], oligodendroglial [5 oligodendrogliomas, 3 anaplastic oligodendrogliomas], and 6 anaplastic oligoastrocytomas tumors. One tumor had been classified as glioneuronal neoplasm. Normal brain was purchased from Stratagene. Stratagene Universal Common Reference was used as reference RNA. The results provide insights into molecular mechanisms and pathways associated with gliomagenesis. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. type: Logical Set Keywords: other
Project description:BackgroundImprovements in brain tumor treatments have led to an increase in the number of young women with brain tumors who are now considering pregnancy. The aim of this study is to evaluate the influence of pregnancy on brain tumor biology.MethodsIn this institutional review board-approved retrospective study, we searched the institution's database for patients with glial brain tumors who were pregnant at the time of diagnosis or became pregnant during the course of their illness. We identified 34 such patients and reviewed their charts to determine each patient's clinical course and pregnancy outcome.ResultsFifteen patients were diagnosed with a primary brain tumor during pregnancy: 3 with glioblastomas, 6 with grade III gliomas, and 6 with grade II gliomas. Pregnancy was terminated in only 2 of these patients, and the remainder delivered healthy babies. Twenty-three patients became pregnant after diagnosis (4 patients were pregnant at diagnosis and again after diagnosis). Of the patients who became pregnant after diagnosis, the 5 with grade I tumors had stable disease during and after pregnancy. However, of the 18 patients with grade II or III gliomas, 8 (44%) had confirmed tumor progression during pregnancy or within 8 weeks of delivery.ConclusionsIn contrast to grade I gliomas, the tumor biology of grades II and III gliomas may be altered during pregnancy, leading to an increased risk of tumor progression. These findings support the need for increased tumor surveillance and patient counseling and for additional data collection to further refine these results.
Project description:The most common primary tumors of the human brain are thought to be of glial cell origin. However, glial cell neoplasms cannot be fully classified by cellular morphology or with conventional markers for astrocytes, oligodendrocytes, or their progenitors. Recent insights into central nervous system tumorigenesis suggest that novel molecular markers might be found among factors that have roles in glial development. Oligodendrocyte lineage genes (Olig1/2) encode basic helix-loop-helix transcription factors. In the rodent central nervous system, they are expressed exclusively in oligodendrocytes and oligodendrocyte progenitors, and Olig1 can promote formation of an chondroitin sulfate proteoglycon-positive glial progenitor. Here we show that human OLIG genes are expressed strongly in oligodendroglioma, contrasting absent or low expression in astrocytoma. Our data provide evidence that neoplastic cells of oligodendroglioma resemble oligodendrocytes or their progenitor cells and may derive from cells of this lineage. They further suggest the diagnostic potential of OLIG markers to augment identification of oligodendroglial tumors.
Project description:Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Characterization of DNA copy number changes in 54 glial brain tumors using a cDNA microarray-based comparative genomic hybridization method. Tumors: 54 fresh-frozen glioma specimens subjected to standard WHO classification. Specimens included astrocytic [3 juvenile pilocytic astrocytomas, 1 low-grade astrocytic glioma, 3 anaplastic astrocytomas, 31 glioblastomas (of these 3 secondary glioblastomas and 2 gliosarcomas)], oligodendroglial [5 oligodendrogliomas, 3 anaplastic oligodendrogliomas], and 7 anaplastic oligoastrocytomas tumors. One tumor had been classified as glioneuronal neoplasm. Human male and female genomic reference DNA was purchased from Promega (Promega, Madison, WI). The results provide insights into molecular genetic changes associated with gliomagenesis.
Project description:Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Characterization of DNA copy number changes in 54 glial brain tumors using a cDNA microarray-based comparative genomic hybridization method. Tumors: 54 fresh-frozen glioma specimens subjected to standard WHO classification. Specimens included astrocytic [3 juvenile pilocytic astrocytomas, 1 low-grade astrocytic glioma, 3 anaplastic astrocytomas, 31 glioblastomas (of these 3 secondary glioblastomas and 2 gliosarcomas)], oligodendroglial [5 oligodendrogliomas, 3 anaplastic oligodendrogliomas], and 7 anaplastic oligoastrocytomas tumors. One tumor had been classified as glioneuronal neoplasm. Human male and female genomic reference DNA was purchased from Promega (Promega, Madison, WI). The results provide insights into molecular genetic changes associated with gliomagenesis. Keywords: other
Project description:The structural complexity of chromosome 1p centromeric region has been an obstacle for fine mapping of tumor suppressor genes in this area. Loss of heterozygosity (LOH) on chromosome 1p is associated with the longer survival of oligodendroglioma (OD) patients. To test the clinical relevance of 1p loss in glioblastomas (GBM) patients and identifiy the underlying tumor suppressor locus, we constructed a somatic deletion map on chromosome 1p in 26 OG and 118 GBM. Deletion hotspots at 4 microsatellite markers located at 1p36.3, 1p36.1, 1p22 and 1p11 defined 10 distinct haplotypes that were related to patient survival. We found that loss of 1p centromeric marker D1S2696 within NOTCH2 intron 12 was associated with favorable prognosis in OD (P = 0.0007) as well as in GBM (P = 0.0175), while 19q loss, concomitant with 1p LOH in OD, had no influence on GBM survival (P = 0.918). Assessment of the intra-chromosomal ratio between NOTCH2 and its 1q21 pericentric duplication N2N (N2/N2N-test) allowed delineation of a consistent centromeric breakpoint in OD that also contained a minimally lost area in GBM. OD and GBM showed distinct deletion patterns that converged to the NOTCH2 gene in both glioma subtypes. Moreover, the N2/N2N-test disclosed homozygous deletions of NOTCH2 in primary OD. The N2/N2N test distinguished OD from GBM with a specificity of 100% and a sensitivity of 97%. Combined assessment of NOTCH2 genetic markers D1S2696 and N2/N2N predicted 24-month survival with an accuracy (0.925) that is equivalent to histological classification combined with the D1S2696 status (0.954) and higher than current genetic evaluation by 1p/19q LOH (0.762). Our data propose NOTCH2 as a powerful new molecular test to detect prognostically favorable gliomas.
Project description:Chromatin immunoprecipitation (ChIP)-seq analyses of transcription factors in clinical specimens are challenging due to the technical limitations and low quantities of starting material, often resulting in low enrichments and poor signal-to-noise ratio. Here, we present an optimized protocol for transcription factor ChIP-seq analyses in human tissue, yielding an ∼100% success rate for all transcription factors analyzed. As proof of concept and to illustrate general applicability of the approach, human tissue from the breast, prostate, and endometrial cancers were analyzed. In addition to standard formaldehyde fixation, disuccinimidyl glutarate was included in the procedure, greatly increasing data quality. To illustrate the sensitivity of the optimized protocol, we provide high-quality ChIP-seq data for three independent factors (AR, FOXA1, and H3K27ac) from a single core needle prostate cancer biopsy specimen. In summary, double-cross-linking strongly improved transcription factor ChIP-seq quality on human tumor samples, further facilitating and enhancing translational research on limited amounts of tissue.
Project description:We used microarrays to identify the expression differences of FKBP5 gene between the pancreatic tumor and normal samples. On average normal samples had more FKBP5 expression compared to tumor samples .Experiment Overall Design: This experiment consists of 36 tumor samples and 16 normal samples; a total of 52 samples. 16 samples consist of both tumor and normal expression data, whereas 20 samples consist of only tumor data.