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Technology Insight: tuning into the genetic orchestra using microarrays—limitations of DNA microarrays in clinical practice

Nature Clinical Practice Oncology volume 3, pages 501–516 (2006)Cite this article

Abstract

Scientific advances in the field of genetics and gene-expression profiling have revolutionized the concept of patient-tailored treatment. Analysis of differential gene-expression patterns across thousands of biological samples in a single experiment (as opposed to hundreds to thousands of experiments measuring the expression of one gene at a time), and extrapolation of these data to answer clinically pertinent questions such as those relating to tumor metastatic potential, can help define the best therapeutic regimens for particular patient subgroups. The use of microarrays provides a powerful technology, allowing in-depth analysis of gene-expression profiles. Currently, microarray technology is in a transition phase whereby scientific information is beginning to guide clinical practice decisions. Before microarrays qualify as a useful clinical tool, however, they must demonstrate reliability and reproducibility. The high-throughput nature of microarray experiments imposes numerous limitations, which apply to simple issues such as sample acquisition and data mining, to more controversial issues that relate to the methods of biostatistical analysis required to analyze the enormous quantities of data obtained. Methods for validating proposed gene-expression profiles and those for improving trial designs represent some of the recommendations that have been suggested. This Review focuses on the limitations of microarray analysis that are continuously being recognized, and discusses how these limitations are being addressed.

Key Points

  • Gene-expression microarrays are tools that can be used to simultaneously measure the level of gene expression of all genes within a cell

  • Recent advances in technology and science are propelling microarray-based tests into the forefront of medicine

  • In the last 5 years, numerous gene-expression profiles predicting prognosis and response to specific therapies for several malignancies have been reported

  • Current limitations in the technology as well as in the biostatistical methods of analysis of the large quantities of data generated from microarray tests predispose the results to misinterpretation

  • Standardization of protocols and validation of current profiles will have to ensure that gene-expression profiles are reliable and reproducible, and therefore ready for clinical implementation

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Figure 1: Key considerations when performing gene-expression profiling using microarray analysis.
Figure 2: Gene-expression profiling using microarray analysis.

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Acknowledgements

We would like to thank L Wessel for advice and critical reading of the manuscript. We thank R Kerkhoven for his artwork for Figure 2.

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Authors and Affiliations

  1. an undergraduate student,

    Ambreen Abdullah-Sayani

  2. a graduate student,

    Jolien M Bueno-de-Mesquita

  3. Head of the Department of Pathology, all at the Netherlands Cancer Institute, Amsterdam, The Netherlands

    Marc J van de Vijver

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  1. Ambreen Abdullah-Sayani
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Correspondence to Marc J van de Vijver.

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Abdullah-Sayani, A., Bueno-de-Mesquita, J. & van de Vijver, M. Technology Insight: tuning into the genetic orchestra using microarrays—limitations of DNA microarrays in clinical practice. Nat Rev Clin Oncol 3, 501–516 (2006). https://doi.org/10.1038/ncponc0587

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