Public databases of the Cancer Genome Anatomy Project were used to quantify the relative gene expression levels in glioblastoma multiforme (GBM) and normal brain by Serial Analysis of Gene Expression (SAGE). Analysis revealed HC gp-39 among the genes with the most pronounced changes of expression in tumor cells. Northern hybridization confirmed the results of computer analysis and showed that enhanced expression of the HC gp-39 gene was mainly in GBMs and occasionally in anaplastic astrocytomas. Neither SAGE nor Northern analysis revealed the presence of HC gp-39 mRNA in the glioblastoma cell line, thus the detection of increased quantities of this mRNA in GBMs may be associated with activated macrophages. Since the numbers of infiltrating macrophages and small vessel density are higher in glioblastomas than in anaplastic astrocytomas or astrocytomas, the HC gp-39 gene can be used as a molecular marker in the analysis of malignant progression of astrocytic gliomas. q

No abstract

Background and Objectives: Our objective was to identify differentially expressed genes involved in the pathogenesis of glioblastoma multiforme (GBM). Methods: Screening of arrayed human fetal brain and human postnatal brain cDNA libraries was performed by differential hybridization with glioblastoma multiforme and human normal brain cDNAs. Results: Repeated differential hybridization of more than 100 cDNA clones selected by primary screening and analysis of RNA from adult normal brain and glial tumors showed 16 nucleotide sequences differentially expressed between normal brain and brain tumors. Among others, decreased content in astrocytic tumors was determined for TSC-22 mRNA corresponding to cDNA in the ICRFp507J1041 clone from human fetal brain cDNA library. Northern blot hybridization of RNA from different human brain tumors showed very low amounts of TSC-22 mRNA in most investigated samples of GBM, anaplastic astrocytoma, and some other tumors. Complete lack of expression of TSC-22 occurred in one sample of anaplastic astrocytoma, as well as in meningioma, brain sarcoma, sarcomatous meningioma, and oligodendroglioma. The differential expression of TSC-22 gene was confirmed by semiquantitative RT-PCR in 15 samples of astrocytomas WHO grade II-IV and three samples of normal brain. Conclusions: Significantly decreased levels of TSC-22 mRNA in human brain and salivary gland tumors and antiproliferative role of TSC-22 strongly suggest a tumor suppressor role for TSC-22.

Screening of human fetal brain cDNA library by glioblastoma (GB) and normal human brain total cDNA probes revealed 80 differentially hybridized clones. Hybridization of the DNA from selected clones and the same cDNA probes confirmed this difference for 38 clones, of which eight clones contained Alu-repeat inserts with increased levels in GB. Thirty clones contained cDNAs corresponding to mitochondrial genes for ATP synthase subunit 6 (ATP6), cytochrome c oxidase subunit II (COXII), cytochrome c oxidase subunit III (COXIII), NADH dehydrogenase subunit 1 (ND1), NADH dehydrogenase subunit 4 (ND4), and mitochondrial 12S rRNA. The levels of all these mitochondrial transcripts were decreased in glioblastomas as compared to tumor-adjacent histologically normal brain. Earlier we found the same for cytochrome c oxidase subunit I (COXI) Serial Analysis of Gene Expression (SAGE) showed lower content of the tags for all mitochondrial genes in GB SAGE libraries and together with our experimental data could serve as evidence of general inactivation of the mitochondrial genome in glioblastoma-the most malignant and abundant form of human brain tumor. q 2004 Published by Elsevier Ireland Ltd.

CD150 (IPO3/SLAM) belongs to the SLAM family of receptors and serves as a major entry receptor for measles virus. CD150 is expressed on normal and malignant cells of the immune system. However, little is known about its expression outside the hematopoietic system, especially tumors of the central nervous system (CNS). Although CD150 was not found in different regions of normal brain tissues, our immunohistochemical study revealed its expression in 77.6% of human CNS tumors, including glioblastoma, anaplastic astrocytoma, diffuse astrocytoma, ependymoma, and others. CD150 was detected in the cytoplasm, but not on the cell surface of glioma cell lines, and it was colocalized with the endoplasmic reticulum and Golgi complex markers. In addition to the full length mRNA of the mCD150 splice isoform, in glioma cells we found a highly expressed novel CD150 transcript (nCD150), containing an 83 bp insert. The insert is derived from a previously unrecognized exon designated Cyt-new, which is located 510 bp downstream of the transmembrane region exon, and is a specific feature of primate SLAMF1. Both mCD150 and nCD150 cDNA variants did not contain any mutations and had the leader sequence. The nCD150 transcript was also detected in normal and malignant B lymphocytes, primary T cells, dendritic cells and macrophages; however, in glioma cells nCD150 was found to be the predominant CD150 isoform. Similarly to mCD150, cell surface expression of nCD150 allows wild type measles virus entry to the cell. Our data indicate that CD150 expression in CNS tumors can be considered a new diagnostic marker and potential target for novel therapeutic approaches.