Depending on patient mix and a laboratory’s financial and technical resources and personnel expertise, selecting one next-generation sequencing (NGS) platform rather than another can be the wisest move. Linnea Baudhuin, Ph.D., Co-Director of the Personalized Genomics Laboratory at Mayo Clinic in Rochester, Minnesota, discusses the options in CAP Today.
According to Dr. Baudhuin, "There are benefits to both targeted NGS and more comprehensive exome and genome analyses. The decision to lean one way or the other is mainly dependent on the clinical context."
In a presentation at the annual scientific meeting of the American Association for Clinical Chemistry, Dr. Baudhuin presented two cases from her own laboratory to illustrate the benefits and shortcomings of targeted NGS testing versus the use of exomes. She focused on inherited (germline) disorders, such as cardiomyopathies and aortopathies, rather than somatic diseases. For tumor (somatic) sequencing, targeted NGS is generally the best approach at this time, she said, because of the need for a fast turnaround and greater depth of coverage.
"A few years ago, it was recommended that all possible genetic testing be done before considering exome," Dr. Baudhuin says. "But I think now, people are choosing exome sequencing more readily than they were before." In her view, this movement comes from the perspective that exome sequencing in the right patient population is a good test. "There are many complex developmental disorders in which it makes more sense to do exome testing first," she says, "rather than ordering a bunch of panels."
According to Dr. Baudhuin's prediction, over the long term, next-generation sequencing will move from targeted panels to exome sequencing to genome sequencing. "We need a few things to happen for our practice to move in that direction," she says.
First, the cost must come down. The cost of the large targeted panels ranges from $1,000 to $5,000, with most falling into the $1,000 to $2,500 range, she says. For clinical exome sequencing, the range is $5,000 to $10,000. Second, the technology has to improve such that exome reagents provide better coverage. Third, variant classification and interpretation tools and skills have to become more effective and streamlined. "When those things come together,” she says, “we will see a lot more exome and genome testing because they are so much more encompassing."