Clinical utility of microarrays: current status, existing challenges and future outlook

Abstract

Microarray-based clinical tests have become powerful tools in the diagnosis and treatment of diseases. In contrast to traditional DNA-based tests that largely focus on single genes associated with rare conditions, microarray-based tests are ideal for the study of diseases with underlying complex genetic causes. Several microarray based tests have been translated into clinical practice such as MammaPrint and AmpliChip CYP450. Additional cancer-related microarray-based tests are either in the process of FDA review or under active development, including Tissue of Tumor Origin and AmpliChip p53. All diagnostic microarray testing is ordered by physicians and tested by a Clinical Laboratories Improvement Amendment-certified (CLIA) reference laboratory. Recently, companies offering consumer based microarray testing have emerged. Individuals can order tests online and service providers deliver the results directly to the clients via a password-protected secure website. Navigenics, 23andMe and deCODE Genetics represent pioneering companies in this field. Although the progress of these microarray-based tests is extremely encouraging with the potential to revolutionize the recognition and treatment of common diseases, these tests are still in their infancy and face technical, clinical and marketing challenges. In this article, we review microarray-based tests which are currently approved or under review by the FDA, as well as the consumer-based testing. We also provide a summary of the challenges and strategic solutions in the development and clinical use of the microarray-based tests. Finally, we present a brief outlook for the future of microarray-based clinical applications.

Keywords: 23andMe; AmpliChip CYP450; AmpliChip p53; MammaPrint; Microarray; deCODE genetics.; navigenics; tissue of tumor origin.

Fig. (1)

Schematic presentation of AmpliChip CYP450 test: from determined genotype, predicted phenotype to optimized drug dose.

Fig. (2)

The outline of the MammaPrint test and subsequent treatment. Adjuvant hormonal therapy should be given to patients with estrogen-receptor-positive disease.

Fig. (3)

An example of Pathwork tissue of origin test report. The test produced a similarity score of >30 for colorectal tissue and <5 for other tissues, indicating that the tumor was originated from colorectal. Fifteen tested tissues are listed on the left.