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Nationwide Children’s studying kids’ genetics for new cancer treatments

Trying to describe genome sequencing, Richard Wilson referred to a 1,000-piece jigsaw puzzle.

Imagine an image of a sailboat atop blue water and surrounded by blue sky, he said.

Then imagine the pieces of that puzzle mixed with the pieces of 10 identical puzzles.

Now, try to put just one of them together.

That, Wilson said, is much like what happens when a scientist pulls data from the DNA of a single person’s genome.

Wilson is the executive director of the Institute for Genomic Medicine at Nationwide Children’s Hospital in Columbus. He opened his labs last week to give hospital employees and others a peek at the machines and researchers who are taking the first steps to help find new cancer treatments, reveal rare diseases and change the way medicine is practiced.

“There’s a whole bunch of cool stuff going on here,” Wilson said. “A lot of what we’re doing is very cutting edge.”

Among the machines he showed off was a sequencer, an instrument that saves scientists from having to dig through all those puzzle pieces.

The $750,000 machine reads DNA that is obtained from a patient’s tissue sample and placed on a “flow cell” that looks much like a microscope slide. The machine pulls information from the DNA, thereby sequencing the patient’s genome — a genome is the complete set of genes or genetic material in a cell or organism.

The sequencing runs for three or four days, sequencing the genomes of four to 16 samples at a time.

“The heart of the operation is instruments like this,” Wilson said. Without them, it would take an army of researchers years and cost $1 billion to read a single genome. At Nationwide Children’s, hundreds of genomes are sequenced every year, at a cost of about $15,000 each.

But that’s just the start. After data are pulled from DNA, the more than 20,000 genes must be analyzed to look for mutations. That’s done by researchers who sit in front of computer screens in the institute’s “dry labs.”

Once analyzed, the information is placed in the hands of other researchers or clinicians who can look for ways to treat specific mutations.

For example, the genomes of eight children with cancerous brain tumors were sequenced this summer, Wilson said. Seven of them received more information about their tumors, with six being given a new chance, taking drugs already found in the pharmacy but previously not used for their conditions.

“Genomics can really allow us to zoom in on exactly what’s gone wrong and maybe come up with a better treatment for the kids that we see,” Wilson said.

That’s called precision medicine, when clinicians tailor care to a patient instead of using a one-size-fits-all approach to cancers and other diseases.

The scale of the institute, and the level of expertise of Wilson and institute co-director Elaine Mardis, make it comparable to only a handful of such centers in the world, said Dr. Sameek Roychowdhury, an assistant professor of medical oncology and a research specialist in genomics and tumor DNA sequencing at Ohio State University’s Wexner Medical Center, which collaborates with Nationwide Children’s.

The institute will make Columbus a leader in genomics and precision medicine, he said, and allow it to attract more grant funding and experts in the field.

“All of these things are going to be affected by this institute,” Roychowdhury said. “It’s really going to be a magnet for change.”

The technology, he noted, is reshaping medicine. It leads to new ways of understanding disease and changes the way doctors diagnose illnesses, offer prognoses and treat patients. Clinicians who were stymied by rare diseases are re-diagnosing people after learning of specific genetic mutations.

For now, the main focus of the institute is cancer patients, and it reviews tissue samples not just from Nationwide Children’s patients but also from Wexner. But the analysis can be done on any patient. One example is a team of researchers that is trying to discover new ways to treat pediatric congenital heart defects.

“You can pretty much fill in the blank with your favorite childhood disease — that’s an opportunity for research,” Wilson said.

Next steps are to figure out how to do things faster so more genomes can be read and analyzed. Getting to more kids is the key, Wilson said.

A robotic machine that processes DNA recently was being tested by Natalie Bir, a technology development specialist.

A researcher can process up to 12 DNA samples a day, but the machine can do eight times that many.

“We can do 96 samples, which means we can put more samples on a sequencer and sequence more patients,” Bir said. “And physicians will be able to request more testing and, in the end, more kids will be able to be helped.”

The future is now, Bir said.

“Our genetic code says a lot about an individual, and I think there are a lot of unknowns about that, and our job is to try to figure out what all that means and help people survive in the end,” she said.

The institute is unique compared with many other places that do genomic testing in that it sequences cancer patients’ entire genome of more than 20,000 genes, instead of just 50 to 100 of the most likely culprits based on diagnoses, Wilson said.

“Using higher level methods … is allowing us to find some things that are much less common and very novel and incredibly informative in terms of what the oncologists need to know to better treat the patients,” he said.

Although the more simple tests are covered by many insurance companies, the entire genome sequencing is not. The institute operates on philanthropic money.

It was opened in 2016 after the recruitment of Wilson and Mardis, who combined their expertise with that of groups already studying genomics at Nationwide Children’s.

“We’ve built that all into what we hope is going to be a real powerhouse for human genomics,” Wilson said.