Abstract

Tumor markers and antigens are normally highly expressed in malignant tissue, but not in the surrounding normal tissue. Serial Analysis of Gene Expression (SAGE) is a technology that counts mRNA transcripts and can be used to find those genes most highly induced in malignant tissues. SAGE produces a comprehensive profile of gene expression and can be used to search for tumor biomarkers in a limited number of samples. Public sources of SAGE data, in particular through the Cancer Genome Anatomy Project, increase the value of this technology by making a large source of information on many tumors and normal tissues available for comparison. Although the perfect tumor-specific gene does not exist, the differences in gene expression between tumor and normal can be exploited for therapeutic or diagnostic purposes.

Highlights

  • During tumor growth, the pattern of expressed genes in the tumor diverges from that of the surrounding normal tissue

  • Simple knowledge of which tumor genes are induced compared with normal tissues can aid in locating clinically useful markers or antigens, even though the molecular basis of the altered expression is typically unknown

  • Serial Analysis of Gene Expression (SAGE) is a sequence-based approach that produces and counts the transcripts expressed within a group of cells [35]

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Summary

Introduction

The pattern of expressed genes in the tumor diverges from that of the surrounding normal tissue. Toxic antibodies immunized to tumor antigens on the cell-surface or in the extra-cellular matrix may kill enough cancer cells to be therapeutic [21] This approach ideally requires the cell surface protein to be uniquely expressed on all the tumor cells, but not expressed in any normal cells that would be in contact with the antibody during treatment. The introduction of large-scale gene expression analysis has been used successfully to classify tumors by RNA expression patterns, in particular using DNA microarrays This has helped further separate aggressive from non-aggressive tumors and in some cases, help predict response to therapy. The transcripts found by SAGE to be induced to high level normally expresses the coded proteins at high levels, making this approach useful for locating candidate tumor antigens, as well. There are several examples that have been published already using SAGE for locating cancer markers and antigens, but the potential for this technology to discover disease biomarkers is just being realized

What is SAGE?
Assessment of SAGE technology
Public sources of SAGE data
Bioinformatics
Verification of genes identified by SAGE
Colon cancer
Ovarian cancer
Tumor vascular endothelium
Brain cancer
Pancreatic cancer
Breast cancer
Findings
Discussion and future goals
Full Text
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