Childhood Cancer Awareness Month Feature: Nationwide Children’s Hospital Aims to Eliminate Inequities Through Cancer Genomics

Elaine R. Mardis, Ph.D.
Co-Executive Director, Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital
Professor of Pediatrics, The Ohio State University College of Medicine 

Large-scale studies of cancer genomes have transformed our understanding of cancer, leading to new treatments, better ways to monitor disease, and improved therapy response and outcome prediction. However, most of these studies lack data on cancers from diverse populations, as these groups are often underrepresented. This gap means there is a crucial opportunity to learn more about common gene mutations or how to predict treatment outcomes for people from minority groups. Leaving this gap unaddressed presents barriers to the National Cancer Plan goal of improving delivery of optimal care, as we determined in a retrospective study of Black patients with acute myeloid leukemia (AML).

At Nationwide Children’s Hospital, and in collaboration with The Ohio State University College of Medicine, we studied the tumor and normal genomes of 100 Black AML patients who received standard chemotherapy in frontline clinical trials offered by the Alliance for Clinical Trials in Oncology (an NCI cooperative group). We found that many of the gene mutations commonly found in White AML patients are also present in Black AML patients but occur at different frequencies. In addition, we identified gene mutations in Black AML patients not reported in studies of primarily White patients. Furthermore, Black patients with gene mutations that have been “good” predictors of cancer progression based on the European LeukemiaNet prognostic index had worse outcomes—for example, NPM1 mutations. The findings from our study suggest a need to reassess how we use gene mutations to predict outcomes in Black patients and adjust therapy regimens, as well as considering adding new genes to testing panels for patients of African ancestry.

Inherited disparities also exist for pediatric, adolescent, and young adult cancer patients, who often lack access to advanced genomic testing that can improve diagnosis and inform optimal care delivery. Ideally, these patients should have both their tumor and constitutional (germline) DNA and tumor RNA characterized to identify underlying genetic cancer predisposition, potential variants to target, and outcome-predictive markers that can guide treatment. To address this disparity and examine the impact of precision diagnosis on outcomes, we partnered with the Children’s Oncology Group (COG) in March 2022 to enroll patients with solid tumors (brain, soft tissue sarcoma, rare cancers, and high-risk neuroblastoma) onto the COG registry study, Project:EveryChild. This work is part of the Childhood Cancer Data Initiative (CCDI) Molecular Characterization Initiative, a program sponsored by NCI that is a collaboration between the childhood cancer community, including COG. 

Our clinical lab has conducted clinical genomic testing on samples from over 208 COG sites to date, providing results to doctors within 14 days of receipt. As of August 2024, more than 3,700 children from 47 states, including Washington D.C. and Puerto Rico, have been evaluated through the CCDI Molecular Characterization Initiative. Importantly, all data are anonymized and made available to researchers through the CCDI Data Ecosystem, maximizing data utility and fueling future discoveries.