dataset
posted on 2023-04-04, 00:22 authored by Kristopher R. Bosse, Anna Maria Giudice, Maria V. Lane, Brendan McIntyre, Patrick M. Schürch, Guillem Pascual-Pasto, Samantha N. Buongervino, Sriyaa Suresh, Alana Fitzsimmons, Adam Hyman, Maria Gemino-Borromeo, Jennifer Saggio, Esther R. Berko, Alexander A. Daniels, Jennifer Stundon, Megan Friedrichsen, Xin Liu, Matthew L. Margolis, Marilyn M. Li, Marni Brisson Tierno, Geoffrey R. Oxnard, John M. Maris, Yael P. Mossé Supplementary Data from Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma
Funding
Damon Runyon Cancer Research Foundation (DRCRF)
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...U.S. Department of Defense (DOD)
Giulio D'Angio Endowed Chair
Patricia Brophy Endowed Chair
Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)
Devaney Family Fund
Band of Parents Foundation
Laney's Legacy of Hope
EVAN Foundation
History
ARTICLE ABSTRACT
Neuroblastoma evolution, heterogeneity, and resistance remain inadequately defined, suggesting a role for circulating tumor DNA (ctDNA) sequencing. To define the utility of ctDNA profiling in neuroblastoma, 167 blood samples from 48 high-risk patients were evaluated for ctDNA using comprehensive genomic profiling. At least one pathogenic genomic alteration was identified in 56% of samples and 73% of evaluable patients, including clinically actionable ALK and RAS–MAPK pathway variants. Fifteen patients received ALK inhibition (ALKi), and ctDNA data revealed dynamic genomic evolution under ALKi therapeutic pressure. Serial ctDNA profiling detected disease evolution in 15 of 16 patients with a recurrently identified variant—in some cases confirming disease progression prior to standard surveillance methods. Finally, ctDNA-defined ERRFI1 loss-of-function variants were validated in neuroblastoma cellular models, with the mutant proteins exhibiting loss of wild-type ERRFI1's tumor-suppressive functions. Taken together, ctDNA is prevalent in children with high-risk neuroblastoma and should be followed throughout neuroblastoma treatment.
ctDNA is prevalent in children with neuroblastoma. Serial ctDNA profiling in patients with neuroblastoma improves the detection of potentially clinically actionable and functionally relevant variants in cancer driver genes and delineates dynamic tumor evolution and disease progression beyond that of standard tumor sequencing and clinical surveillance practices.See related commentary by Deubzer et al., p. 2727.This article is highlighted in the In This Issue feature, p. 2711
