Expression of multiple larger-sized transcripts for several genes in oligodendrogliomas: potential markers for glioma subtype.
Astrocytomas and oligodendrogliomas are two brain tumors that follow different clinical courses. Although many of these tumors can be identified based on standard histopathological criteria, a significant percentage present notable problems in diagnosis. To identify markers that might prove useful in distinguishing glioma subtypes, we prepared and analyzed cDNA libraries for differential expression of genes in an astrocytoma (grade II), an oligodendroglioma (grade II), and a meningioma (benign). The tumor libraries were compared by sequencing randomly selected clones and tabulating the expression frequency of each gene. In addition to identifying several genes previously reported or expected to be differentially expressed among these tumors, several potential new brain tumor markers were identified and confirmed by Northern blot analysis of a panel of brain tumors. A surprising result of this analysis was the observation that several larger-sized transcripts for various genes were predominantly expressed in the oligodendroglioma tumors, when compared to the other brain tumors or in non-tumor gray matter. These findings are consistent with different pre-mRNA splicing patterns observed between oligodendrogliomas and astrocytomas. In support of this hypothesis, our screen revealed significantly higher levels of two hnRNP A1 transcripts in oligodendrogliomas. hnRNP A1 is a component of the spliceosome whose expression levels affect splice site selection in vivo. The preferential expression of larger-sized transcripts for several genes in oligodendrogliomas may be useful for distinguishing astrocytic and oligodendroglial gliomas.
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Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Joh
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Pin
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Schiller
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Prange
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Burger
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Schiller
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D001254:Astrocytoma / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D005910:Glioma / Q000145:classification* / Q000235:genetics; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008970:Molecular Weight; D009837:Oligodendroglioma / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D017381:Spliceosomes / Q000378:metabolism; D013382:Subtraction Technique
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012261:Ribonucleoproteins