Dartmouth’s Tsongalis Tracks Elusive Diagnoses
with Personalis® Exome Services
Greg J. Tsongalis, Ph.D.
In his work directing the clinical molecular pathology labs at the Dartmouth Hitchcock Medical Center, Greg Tsongalis, Ph.D. seeks to apply molecular techniques to diagnostic questions that are not adequately addressed by traditional laboratory methods. His labs provide DNA- and RNA-based testing for everything from genetic diseases and infectious diseases to oncology and pharmacogenomics.
In the last couple of years, his team has been exploring next-generation sequencing, typically through referral labs, as a way to consolidate some of the testing they were doing. Even though NGS has brought down the cost of doing sequencing and made gene panels more cost effective in some cases than individual gene tests, sending out panels of genes to be sequenced can add up quickly, especially when results are coming back negative with each round.
“Going through these lists of panels can cost up to $30,000 or $40,000 per patient,” Tsongalis says.
To avoid such high costs, and improve their ability and efficiency in diagnosing hard cases, Dartmouth scientists and clinicians turned to the Personalis ACE clinical exome service.
“It turns out that cost-wise it’s a no brainer. It’s much, much cheaper to do a whole exome sequence through Personalis than it is to run multiple panels individually on any of these patients,” Tsongalis adds.
But to make sure they were betting on the right service provider, they started by giving the company a few difficult and unresolved cases.
“These were patients our medical teams have been working with for a while now and just couldn’t come up with a diagnosis despite the tens of thousands of dollars that had been spent on genetic testing,” Tsongalis says.
“In each of the cases, Personalis blew us away because they came up with findings of diseases and syndromes that we weren’t even thinking about.”
In one case, he says, “We threw them a curve ball. We were doing some work with a village in Honduras and we had DNA samples from a couple of kids there who have been seen for the last 10 years by clinicians all over the world. No one could identify the condition that these kids had.”
“With the Personalis results, we were able to identify the mutation in the gene that is associated with homocystinuria and causes significant mental retardation and malformations,” he says.
“It showed the power of the testing,” Tsongalis adds, noting that without the correct diagnosis, “lots patients are being managed for a condition they don’t have.”
Tsongalis now has an agreement in place to send Personalis these tough cases, with hopes that exome sequencing will be able to resolve genetic mysteries and end the diagnostic odyssey for parents and children. But he remarks that it’s not just any exome sequencing that will do. “I could do a whole exome in my lab for $400 to $500 if I wanted to. The problem is that we don’t have the infrastructure to do the data analysis,” he says.
“There are other labs that are offering clinical exome sequencing, but they are not as cost competitive and I don’t think the quality of the product is as good.”
What sets Personalis apart is its unparalleled coverage of exonic sequence, for starters. “The proprietary sequencing chemistry they developed allows them to cover a lot more of the exome than the standard chemistry for NGS,” Tsongalis says. “You can miss mutations with other assays that don’t cover a particular region well enough.” He adds that the company’s pipeline for annotation and curation makes a difference in the final product as well.
As an expert pathologist, Tsongalis knows firsthand the importance of crafting a report to present data clearly to physicians. He says that the report he gets from Personalis meets his exacting specifications. “The report format is comprehensive, but very easy for people to understand,” he says. That’s a huge benefit when it comes to a provider trying to understand what was done and what the results are.”
Based on his experience with the ACE clinical exome sequencing service, Tsongalis says he would recommend Personalis to his peers.
“It’s a spectacular service with a lot of benefits. For academic hospitals like ours, we have a lot to learn from labs like Personalis.”
And Tsongalis is just getting started. “I’m looking forward to being able to run a whole lot more patient samples with Personalis and see what other types of things we can find that we weren’t really thinking about,” he says.