There’s a lot of talk about precision medicine in cancer these days. Using DNA information from cancers to develop targeted medical treatment is such an exciting concept that it gets the popular imagination stirring. However, we’re not at a point right now where we can match every gene mutation to a new cancer treatment.

Cost, for one, has been prohibitive in taking precision medicine to the next level. Another piece of the puzzle has been communication and sharing of research information. But St. Jude Children’s Research Hospital has been building a critical infrastructure of oncologists, geneticists, pathologists and computational biologists, allowing a new level of interdisciplinary collaboration. Thanks to this dedicated team, a new comprehensive genome study means the next generation of targeted cancer treatment isn’t far away.

Delving deeper

Jinghui Zhang, Ph.D., who chairs the Department of Computational Biology on the computing-oriented side of the team, said she and her colleagues realized early on that they must consider the full genome of pediatric cancer.

“We recognized a lot of the important mutations were in the form of genome structural changes, like copy number, rearrangements and fusion events,” says Zhang. The team knew they’d have to start taking a deeper look by comparing the tumor and normal genomes if they were going to figure out what makes cells go bad. “We realized,” she says, “that for a clinical implementation for pediatric cancer, we had to incorporate the whole genome.”

Zhang’s team has built novel computational pipelines across multiple platforms for cross-validation, manipulation and classification of DNA variants, providing one of the richest databases in pediatric oncology research.

“Nowhere else is the methodology or the computational approach as comprehensive as what’s going on here,” says Kim E. Nichols, M.D., who directs the Cancer Predisposition Division and spearheads the team’s clinical efforts. Many doctors in clinical genomics are performing exome testing, which accounts for only 3 percent of the genome.

But something in that remaining 97-plus percent of the genome may crack the code of an individual’s cancer. “Everybody’s cancer is a little bit different,” says Nichols. “It’s only by learning what makes an individual cancer tick that we can optimize future treatments.”

“‘We’re building a cloud-based data platform so that people all over the world can have access to this type of data.’”

Increasing precision

Nichols, Zhang and their colleagues at St. Jude are encouraged by some of the clinical applications their research has already had.

“A handful of children have had their treatment modified according to the results generated through this study,” says Nichols, “and we’ve had a couple of excellent outcomes.”

The team’s unique combination of clinical as well as computation methods is quickly developing one of the richest raw databases in the world of oncology. Hoping this will form the bedrock of further studies, St. Jude plans to make all of the data publicly available to researchers around the globe.

“We’re building a cloud-based data platform so that people all over the world can have access to this type of data,” says Zhang, who is optimistic about the potential for combining her team’s data with what other researchers may have already collected.

The next breakthrough may be discovered anywhere, perhaps in an unlikely place in a patient’s genes. “It could be a different diagnosis,” says Zhang, “or provide a better understanding of the disease, or lead to a novel target that people haven’t recognized.”

But it’s not going to be an overnight project. Meanwhile, patients and their families may benefit from experimental treatments, as well as from knowing they’re doing their part in saving lives in the future. And researchers will have more data at their disposal to continue the fight.

“We can help set the stage for incorporation of genomics into the future care of children with cancer,” says Nichols. “St. Jude wants to be a leader, taking all these groups forward in their understanding of the molecular underpinnings of childhood cancer and cancer risk.”