Neuroblastoma (NBL)

Overview

Neuroblastoma (NBL) is the most common extracranial solid tumor in children, arising from neural crest progenitor cells. High-risk neuroblastoma carries poor prognosis despite multimodal therapy including chemotherapy, surgery, RT, and 131I-MIBG targeted radiotherapy. Intra-tumoral heterogeneity is a recently appreciated feature of neuroblastoma and a focus of active investigation; the tumor’s low mutational burden makes it tractable for mechanistic radiobiology study.

Cohorts in the corpus

  • ROBIN KIDSROBIN COG ANBL1531 cooperative trial (Harvard University and University of California, San Francisco) — accrual complete; frozen tissue from baseline and post-treatment second-look surgical samples obtained for single-cell spatial profiling (Xenium 10x Genomics). PMID:41941260
  • KIDSROBIN NLP cohort — 7,597 clinical notes from 182 NBL patients secured for natural language processing studies. PMID:41941260
  • 11 neuroblastoma tumors spanning INRG risk groups and INSS stages (5 high-risk MYCN-amplified/11q-deleted, 1 intermediate, 5 low-risk), 3 postnatal human adrenal glands, and 5 mouse adrenal glands; 4,224 single nuclei sequenced (3,212 high-quality) by Smart-Seq2 snRNA-seq. External validation in a 498-sample SEQC bulk RNA-seq cohort and 172-sample NCI TARGET cohort. PMID:34493726

Recurrent alterations

No corpus-specific gene-level variant frequencies are reported; the focus is on intra-tumoral heterogeneity and treatment response at single-cell resolution.

  • NBL is noted for low mutational burden, making it a genetically simple model alongside DMG for mechanistic RT response research. PMID:41941260
  • High-risk tumors are characterized by undifferentiated nC3 cluster cells overexpressing MYCN, ALK, NTRK2 (TRKB), BCL11A, TP63, and mesenchymal markers PRRX1/YAP1/PDGFRA; low-risk tumors are dominated by noradrenergic clusters expressing NTRK1 (TRKA), TH, DBH, PHOX2A/PHOX2B. PMID:34493726
  • Chromosomal alterations in high-risk nC3 cells: recurrent 17q gain, 1p loss, 11q loss (confirmed by inferCNV and microarray in samples K87, K10, 23, K55, K3). PMID:34493726
  • nC3 undifferentiated signature correlates with age-at-diagnosis (FDR = 8.12×10⁻³¹) and poor survival in 498-sample SEQC cohort (Kaplan-Meier Bonferroni-corrected p <0.01); noradrenergic nC7/nC8 signatures associate with better outcome. PMID:34493726
  • LC-MS/MS proteomics of 15 neuroblastoma tumors stratified by MYCN status revealed distinct proteomic signatures distinguishing MYCN-amplified from non-amplified tumors PMID:22367537
  • CCLE pharmacogenomic profiling included neuroblastoma cell lines among 947 lines tested across 24 drugs, enabling genotype-response correlation analyses PMID:22460905
  • WES/WGS of 240 neuroblastoma tumors identified ALK, PTPN11, and ATRX as key recurrently mutated genes; low overall somatic mutation rate with enrichment in RAS-MAPK pathway PMID:23334666
  • Comprehensive genomic analysis of neuroblastoma identified recurrent driver alterations including MYCN amplification and ALK mutations with implications for targeted therapy PMID:26466568
  • PIPseq cohort included 4 neuroblastoma cases; MYCN amplification + 1p/11q LOH + 17q gain used for risk-based therapy stratification; ATRX T1747fs identified as poor-prognosis marker; CDK4/MDM2 co-overexpression enrolled one patient on the NEPENTHE trial (NCT02780128); NRAS and KRAS activating mutations also identified PMID:28007021

Subtypes

High-risk NBL is the focus of KIDSROBIN; no further subtype stratification in the corpus.

  • High-risk neuroblastoma (typically children >18 months) contains an undifferentiated nC3 cluster transcriptionally resembling a novel NTRK2+/CLDN11+ postnatal human cholinergic progenitor unique to human adrenal gland (absent in mouse); low-risk tumors resemble noradrenergic/chromaffin cells. These may represent two distinct disease entities rather than a single spectrum. PMID:34493726

Therapeutic landscape

  • ROBIN KIDSROBIN center (U54 CA274516; Harvard University and UCSF) uses Xenium single-cell spatial profiling on baseline and post-131I-MIBG second-look surgical NBL samples to identify cell populations differentially depleted or enriched following 131I-MIBG therapy. PMID:41941260
  • ctDNA nucleosome positioning studies performed at baseline and after 131I-MIBG therapy identified differential changes in transcription factor profiles in samples with subsequent ctDNA rises — candidate biomarkers of response. PMID:41941260
  • Serum miRNA profiling following 131I-MIBG therapy identified a number of differentially modulated miRNAs as candidate response/resistance biomarkers. PMID:41941260
  • Paired 123I-/131I-MIBG diagnostic scans and SPECT/CT images analyzed to estimate tumor-absorbed dose per unit administered activity — enabling dosimetry-based understanding of differential outcomes after 131I-MIBG. PMID:41941260
  • The KIDSROBIN team notes that insights from infrequent pediatric cancers including NBL have historically proven generalizable to more common adult cancers. PMID:41941260
  • NTRK1 (TRKA) vs. NTRK2 (TRKB) expression are mutually exclusive outcome biomarkers at single-cell level, validated by RNAscope ISH: NTRK1+ low-risk tumors have favorable prognosis while NTRK2+ undifferentiated cells associate with poor outcome. PMID:34493726
  • nC3 transcriptional signature stratifies 498 SEQC patients by survival; the nC3 cluster gene program enriches for DNA damage/repair and cell motility GO terms. PMID:34493726

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22367537

This page was processed by crosslinker on 2026-05-14. - PMID:22460905

This page was processed by crosslinker on 2026-05-14. - PMID:23334666

This page was processed by crosslinker on 2026-05-14. - PMID:26466568

This page was processed by crosslinker on 2026-05-14. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14.