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Technology platforms for pharmacogenomic diagnostic assays

Nature Reviews Drug Discovery volume 3, pages 749–761 (2004)Cite this article

Key Points

  • The application of genetic, genomic and proteomic technologies to the development of in vitro molecular diagnostics provides many opportunities for improving choice of therapy and the prediction of drug response.

  • The first examples of in vitro diagnostics designed to aid therapeutic decisions are making their way towards regulatory approval and routine use in the clinic, and this article reviews some of the relative strengths and limitations of the most widely used technologies and platforms for such diagnostics.

  • The following assay formats and platforms, which are commonly used and currently automated, or that have near-term automation potential, are described: assays using TaqMan probes, assays using hybridization probes, assays using Invader probes, bead-based multiplex genotyping, and high-density microarrays for genotyping.

Abstract

Rapid advances in the understanding of genomic variation affecting drug responses, and the development of multiplex assay technologies, are converging to form the basis for new in vitro diagnostic assays. These molecular diagnostic assays are expected to guide the therapeutic treatment of many diseases, by informing physicians about molecular subtypes of disease that require differential treatment, which drug has the greatest probability of effectively managing the disease, and which individual patients are at the highest risk of experiencing adverse reactions to a given drug therapy. This article reviews some of the relative strengths and limitations of the most widely used technologies and platforms for such assays.

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Figure 1: Genotype analysis approaches: TaqMan probes.
Figure 2: Genotype analysis approaches: hybridization probes.
Figure 3: Genotype analysis approaches: Invader assay.
Figure 4: Bead-based multiplex genotyping using allele-specific primer extension.
Figure 5: Oligonucleotide microarray-based genetic variation detection or gene-expression analysis.
Figure 6: High-density oligonucleotide microarray probe-tiling approaches for genotyping.
Figure 7: Probe-tiling approach for re-sequencing p53.
Figure 8: Affymetrix oligonucleotide microarray probe strategy for differential gene-expression analysis.

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Acknowledgements

The author wishes to thank J. Flanagan for assistance in preparing this manuscript, and G. Beer for providing CYP2C9 four-colour genotyping results.

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Authors and Affiliations

  1. Pharmacogenetics Department, Roche Molecular Systems, 4300 Hacienda Drive, Pleasanton, 94588, California, USA

    Walter H. Koch

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  1. Walter H. Koch
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W.K. is employed by Roche Diagnostics and is engaged in the research and development of pharmagenomics assays.

Related links

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DATABASES

Entrez Gene

ABL

BCR

CFTR

CYP2C9

CYP2C19

CYP2D6

EGFR

ERBB2

factor II

factor V

MDM2

NAT2

p53

TPMT

National Cancer Institute Cancer Topics

Chronic myelogenous leukaemia

FURTHER INFORMATION

CYP2D6 allele nomenclature

Guidance for Industry: Pharmacogenomics Data Submissions

Pharmacogenetics Research Network

Roche 510(k) summary

TM Bioscience Product page

Glossary

SINGLE-NUCLEOTIDE POLYMORPHISM

A substitution of one base pair at a given position in genomic DNA.

CAPILLARY ELECTROPHORESIS

An adaptation of traditional slab gel electrophoresis to a capillary format.

MALDI-TOF MASS SPECTROMETRY

A technique that enables mass spectrometric analyses of biomolecules including proteins and nucleic acids.

PSEUDOGENE

DNA sequence similar to a homologue normal gene but that seems to have no function.

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Koch, W. Technology platforms for pharmacogenomic diagnostic assays. Nat Rev Drug Discov 3, 749–761 (2004). https://doi.org/10.1038/nrd1496

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