Next-gen sequencing (NGS), the media-friendly moniker for automated massively parallel DNA or RNA sequencing technology, has made the leap from a powerhouse tool for molecular biology research and drug discovery and development to the clinical arena.
Not an easy feat for a complex, expensive technology that generates huge amounts of data requiring intensive analysis and interpretation.
The first next-gen sequencer to receive FDA clearance is the Illumina MiSeqDx system, with other NGS instruments hot on its heels. NGS-based diagnostic tests and clinical research tools are already beginning to transform fields such as prenatal testing and oncology, even as predictions for the scope of their applicability continue to broaden.
In a Perspective piece published December 19, 2013 in the New England Journal of Medicine, Francis Collins, M.D., Ph.D., and Margaret Hamburg, M.D., wrote about the first FDA authorization of a NGS instrument: “Clinicians can selectively look for an almost unlimited number of genetic changes that may be of medical significance. Access to these data opens the door for the transformation of research, clinical care, and patient engagement.”
Illumina designed the MiSeqDx system specifically for clinical laboratories, making it affordable and easy to use to broaden its applicability.
“At about the $10,000 threshold we started to see early clinical adoption of next-gen sequencing,” says Greg Heath, Ph.D., svp of in vitro diagnostics at Illumina. Initial applications in rare inherited diseases in children and end-stage cancer were driven primarily by medical need, and technological advances expanded the use of NGS into the area of noninvasive prenatal testing for aneuploidies, bringing with it a great deal of support from the medical community and healthcare reimbursers, according to Dr. Heath.
“I think NGS will displace a lot of PCR-based tools,” predicts Dr. Heath.
The most prominent emerging areas for clinical NGS growth, in his view, include genetic disease, with a particular emphasis on reproductive genetics, and oncology, in which “certain unique performance characteristics of the technology will make it possible to solve some of the fundamental problems in cancer,” such as the heterogeneity of tumors and the difficulty of working with FFPE samples.
Other clinical applications where NGS may have a near-term impact are in transfusion and transplantation medicine. A bit farther off, applications will likely emerge related to methylation in cancer and immunosequencing.