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RNA Reference Materials for Gene Expression Studies

Counterpoint: RNA Metrology: Forecast Calls for Partial Clearing

University of Chicago Pathology, University of Chicago Hospitals, Hospital Mailcode MC0004, 5841 S. Maryland Ave., Chicago, IL 60637, Fax 773-702-6268

The first 20% of the full text of this article appears below.

Microarrays were first applied to experimental studies of gene expression, but newer microarray applications, such as comparative genomic hybridization, have evolved and preceded it to clinical introduction. Challenges to clinical use include potentially dramatic biological changes in gene expression as a result of preanalytic variation in patient and sample handling, analytical variation resulting from the complex assay process, and daunting analytical and statistical problems in simultaneous measurement of thousands of signals ranging over several orders of magnitude.

Arrays come in many formats, including chips, slides, microfluidic devices, and beads. They differ in the sets of genes assayed and in the probe sequences used to assay for a given gene. Some systems hybridize the sample and control to the same array, using two-color labeling, whereas another system hybridizes the sample and control to separate arrays. As a result, formats have incommensurable merits and often incommensurable data. Published information comparing formats are too limited for conclusions other than that data interchange might be feasible (1)(2).

This flowering of ingenuity is acceptable for hunting candidate genes with one format and verifying results by more common techniques, but for clinical applications, this variety is an obstacle. The typical application envisions a multiparametric "gene-expression signature" in which the expression patterns for many genes are combined to generate a "classifier" for diagnosis or prognosis. Laboratory 1, which uses array system brand A, publishes a well-designed study showing that a gene-expression signature distinguishes benign from malignant omphalomas. How should Laboratory 2, which uses brand X, adapt the "signature"? Clinical studies are also hampered by lack of well-defined . . . [Full Text of this Article]