NCI Launches Pediatric Molecular Characterization Initiative

As part of the Childhood Cancer Data Initiative, the NCI has launched the Molecular Characterization Initiative to provide tumor sequencing to children, adolescents, and young adults with central nervous system cancers receiving care at Children's Oncology Group (COG)–affiliated hospitals. By examining tissue at a molecular level, oncologists can make a more precise diagnosis and may determine what's driving tumor growth.

In addition, data from the Molecular Characterization Initiative will be used to assess patients’ eligibility to participate in a clinical trial at one of more than 200 COG institutions, which could improve care for all patients; COG is the largest NCI-supported children's cancer research group.

With the rollout of the initiative, about 3,000 eligible children, adolescents, and young adults will have their tumors sequenced.

“They'll have a consistent, most state-of-the-art assay,” says Ted Laetsch, MD, who leads the Developmental Therapeutics Program at Children's Hospital of Philadelphia in Pennsylvania. “It allows patients, particularly at smaller institutions, who may not have had access to this kind of sequencing before, to get this testing done.”

Alejandro Sweet-Cordero, MD, director of the Molecular Oncology Initiative at the University of California, San Francisco, agrees. “I think this is a great opportunity to really level the playing field and make this kind of cutting-edge molecular diagnostics available to all patients, not just those that are at [large] centers” that have the resources to offer sequencing to their patients, he says. Testing through the Molecular Characterization Initiative is free.

Testing will include methylation analysis, RNA fusion analysis, and whole-exome sequencing. Methylation refines the diagnosis of the tumor through examination of the methyl groups on DNA, which is particularly helpful for brain tumors. Incorporating RNA analysis helps identify common chromosomal fusions that contribute to pediatric cancer development, which traditional molecular assays typically cannot detect. Whole-exome tumor sequencing identifies mutations that may drive the cancer and be potential drug targets, whereas whole-exome sequencing of blood picks up germline alterations that can predispose children to cancer. Data will be kept in a central repository and made accessible to other researchers.

For now, the Molecular Characterization Initiative is restricted to people 25 and younger with brain tumors, which can be challenging to diagnose accurately.

“There has been evolution of diagnosis across all types of cancer but perhaps it's been the most dramatic in pediatric brain tumors,” says Douglas Hawkins, MD, COG group chair. Previously, categorization of tumors was heavily dependent on how tissue looked under a microscope, but “if you want to characterize pediatric brain tumors today, you really need to have the molecular data.”

By the end of 2022, the Molecular Characterization Initiative will start analyzing soft-tissue sarcomas and other rare tumors. Later, COG leaders want to expand the program to include recurrent cancers.

“The momentum that stands on this pediatric initiative is so strong,” notes Brigitte Widemann, MD, chief of the Pediatric Oncology Branch at the NCI. “There is a strong advocacy community for kids with cancer, including their parents and caregivers.”

Depending on what the initiative achieves, a similar program could be developed for more patients. “If we figure this out for pediatric cancers, it will be applicable to the adult cancers as well,” she said. “I would think that would be the plan especially for tumors of unmet need.” –Natalie DiDomenico

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