Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High‑Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study
ALK and RAS pathway aberrations confer inferior outcomes in high‑risk neuroblastoma patients, indicating a need for novel therapeutic approaches.
Relapsed high‑risk neuroblastomas are enriched for targetable mutations in ALK and RAS‑MAPK pathways, yet the prognostic effect of these aberrations and relevance of subclonal mutations at diagnosis remain undefined. We describe the spectrum and clinical significance of clonal and subclonal pathogenic alterations in high‑risk neuroblastoma. A focused high‑risk neuroblastoma sequencing panel was applied to 242 pre‑therapy tumors from patients enrolled on the phase III trial Children’s Oncology Group ANBL0532 to assess the effect of clonal and subclonal mutations on event‑free survival (EFS) and overall survival (OS).
This study demonstrates the importance of risk‑stratified management of patients with high‑risk neuroblastoma based on the molecular alterations present at diagnosis and highlights the need to identify innovative therapies for patients with ALK, RAS‑MAPK, and TP53 aberrations.
Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.
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