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

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.

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Com par i son of gene ex pres sion pro files in hu man nor mal brain and glioblastoma us ing SAGE da ta base revealed 129 genes with 5-fold dif fer ence of ex pres sion level in glioblastoma (P£0.05), 85 of them were down-reg u lated. The num ber of genes with 5-fold down-reg u lated ex pres sion is less in the dif fuse and anaplastic astrocytomas. Five-fold de crease of the ex pres sion in the dif fuse astrocytoma and nearly the same ex pres sion lev els in the anaplastic astrocytoma and glioblastoma were re vealed for 9 genes only. For over whelm ing ma jor ity of in ac ti vated genes in the low-grade astrocytoma the ex pres sion level de creased pro gres sively in the sub se quent stages of ma lig nant pro gres sion of astrocytoma. Ex pres sion lev els of some genes were very low or un de tect able in glioblastoma, the most ag gres sive brain tu mour. The de creased expres sion of se lected genes in glioblastoma was con firmed by North ern anal y sis and RT-PCR. Some genes, de scribed in this work, may en code the tu mour suppressors and their de creased ex pres sion may play an impor tant role in ini ti a tion and pro gres sion of hu man glioma.

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