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Identification of cell surface markers and astrocytoma associated genes


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Website: http://www.biomedcentral.com/1471-2407/4/39/abstract

Posted on: 07/26/2004

Identification of cell surface markers and astrocytoma associated genes

[Note - full text of article is available free - click on the above link]

Kathy Boon , Jennifer B Edwards , Charles G Eberhart and Gregory J Riggins

BMC Cancer 2004, 4:39 doi:10.1186/1471-2407-4-39

Published 21 July 2004

Abstract (provisional)

Background

Despite many efforts the treatment options for the invasive astrocytic tumors are still limited to surgery and radiation therapy, with most chemotherapy regimens showing little or no increase in survival. The generation of Serial Analysis of Gene Expression (SAGE) profiles for the various tumor types is expected to aid in the identification of tumor-associated genes and highly expressed cell surface genes as therapeutic targets. This data format allows easy dissemination of expression profiles that can be used in conjunction with a growing SAGE cancer database.

Methods

We generated and analyzed the SAGE transcription profiles of 24 primary grade II, III and IV astrocytomas [1]. These profiles were produced as part of the Cancer Genome Anatomy Project's SAGE Genie [2], and were used in a in silico search for candidate therapeutic targets by comparing astrocytoma to normal brain transcription. Real-time PCR and immunohistochemistry were used for the validation of selected candidate target genes in 2 independent set of primary tumors.

Results

A restricted set of tumor-associated genes was identified for each grade that included genes not previously associated with astrocytomas (e.g. VCAM1, SMOC1, and thymidylate synthetase), with a high percentage of cell surface genes. Two genes with available antibodies, Aquaporin 1 and Topoisomerase 2A, showed protein expression consistent with transcript level predictions.

Conclusions

This survey of transcription in malignant and normal brain tissues reveals the small subset of human genes that are activated in malignant astrocytomas. In addition to providing insights into pathway biology, we have revealed and quantified expression for a significant portion of cell surface and extra-cellular astrocytoma genes.




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