ARID1B alterations identify aggressive tumors in neuroblastoma

Oncotarget. 2017 Jul 11;8(28):45943-45950. doi: 10.18632/oncotarget.17500.


Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

Keywords: ALK; ARID1B; MYCN; neuroblastoma; sequencing.

MeSH terms

  • Computational Biology / methods
  • DNA Copy Number Variations
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Genetic Variation*
  • Genomics / methods
  • Humans
  • Mutation
  • Neuroblastoma / drug therapy
  • Neuroblastoma / genetics*
  • Neuroblastoma / mortality
  • Neuroblastoma / pathology*
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Survival Analysis
  • Transcription Factors / genetics*


  • ARID1B protein, human
  • DNA-Binding Proteins
  • Transcription Factors