DNA sequencing project could lead to treatments for deadly childhood cancers

(© Micah Young)

U.S. scientists announced the largest-ever release of comprehensive human cancer genome data on Tuesday, in a push to speed progress in treating childhood cancers and other diseases.

As part of the ongoing Pediatric Cancer Genome Project, researchers from St. Jude’s Children’s Research Hospital, in collaboration with the Genome Institute at Washington University School of Medicine, sequenced the entire DNA, or genome, of 520 normal and tumor tissue samples from 260 child cancer patients.

St. Jude’s researchers are using the gene sequences to determine the differences between normal cells and cancer cells and to fully understand the genetic origins of the most deadly childhood cancers.

“Early on, target gene sequencing only looked at the part of the genome of interest…We knew in pediatric tumors, there are a large number of structural alterations, and [less comprehensive] approaches could not detect those abnormalities,” Dr.  James Downing, the St. Jude scientific director who leads the project, told FoxNews.com.

The information Downing and his team released more than doubles the volume of previous data available and can be freely accessed by scientists worldwide.  The researchers hope the data will prove useful to both cancer researchers and to scientists studying other diseases as a baseline ‘dictionary’ of genetic mutations and pathways involved in common diseases.

Previous federally-funded projects have focused almost exclusively on cancers that affect adults, which are fundamentally different than those that affect children, according to Downing.

“We looked at the landscape and felt a focused effort was needed that explored the genomics of pediatric cancers in order to better diagnose and treat those cancers,” he said.  “…We decided to really focus on the pediatric cancers in which we have made the least progress in treating or know the least about the underlying genetics.”

The cancers sequenced mostly included an equal distribution of brain, bone and blood cancers that have notoriously poor treatment rates.

“There’s this urgency because children are dying of cancer – it’s the leading cause of death due to disease,” Downing said.

While massive strides have been made in the fight against pediatric cancers – for example acute lymphoblastic leukemia (ALL), which mere decades ago had only a 5 percent chance of a cure, now has a 90 percent chance of a cure – there are still certain subtypes that have much poorer outcomes.

“A particular subtype of ALL discovered in 2009, known as early T-cell progenitor ALL, only has a 20 percent cure rate,” Downing said.  “Those patients do extremely poorly.”

However, with the sequencing project, researchers realized the ALL subtype may have a much different structure than scientists once thought  -- which could radically change clinical treatment of the disease.

“The punch line is, we’re probably treating this tumor wrong,” Downing said.  “We thought, with its particular lineage, we should treat it with a therapy developed against lymphoid leukemia.  Now, looking at the data, it says that the tumor really has more resemblance to stem cell or myeloid leukemia.”

Thanks to the finding, studies are already being designed to revamp treatment of early T-cell progenitor ALL in order to incorporate myeloid therapy.

“It raises the possibility that treating the tumor with this new therapy may lead to a better chance of a cure,” Downing said.  “Whether or not it leads to an improvement, the project really is having a direct impact on how we think about these diseases and how we treat them.”

The Pediatric Cancer Genome Project launched in early 2010 and is the world’s largest and most expensive investment to date in sequencing childhood cancers, costing an estimated $65 million.  By the end of the three-year privately-funded project, researchers expect to sequence more than 1,200 genomes.

The ultimate goal, according to Downing, is to move toward personalized therapy for every child cancer patient.

“The Pediatric Cancer Genome Project is more successful than I could have possibly imagined,” Downing said.  “We’re gaining insights on every type of tumor, and I’m convinced it will influence the way we diagnose and treat pediatric patients.  The data is becoming an important resource for the entire field.

“I think over the next five to ten years, it will transform the way we think about, approach and treat cancer,” he added.