Chromosomal instability degrades developmental phenotypes essential for anti-GD2 immunotherapy outcomes in high-risk neuroblastoma.

ABSTRACT: High-risk neuroblastoma (HR-NBL) is a pediatric malignancy that arises during sympathoadrenal development and expresses the surface disialoganglioside GD2. Monoclonal anti-GD2 immunotherapy is a mainstay of HR-NBL treatment; however, it is associated with severe toxicities. Genomic correlates of outcomes following multimodality therapy containing anti-GD2 immunotherapy are limited. We profile 840 tumors and identify actionable ALK gene fusions in HR-NBL. We leverage fetal sympathoadrenal single-cell RNA sequencing to characterize patients with improved post-multimodality outcomes. We demonstrate that patients with improved outcomes have tumors that upregulate noradrenergic and metabolic phenotypes characteristic of mature sympathoblasts-a fetal sympathoadrenal cell population. We show that

SUBMITTER: Rebernick RJ 

PROVIDER: S-EPMC12629816 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature