Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma

Nat Genet. 2013 Jan;45(1):12-7. doi: 10.1038/ng.2493. Epub 2012 Dec 2.


Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma, we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases) and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average, each tumor had 19 somatic alterations in coding genes (range of 3-70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of the chromatin-remodeling genes ARID1A and ARID1B were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight the dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of patients with neuroblastoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Child
  • DNA Copy Number Variations
  • DNA-Binding Proteins / genetics*
  • Exome
  • Gene Expression Profiling
  • Gene Order
  • Genomics
  • Humans
  • Mutation*
  • Neuroblastoma / genetics*
  • Neuroblastoma / mortality
  • Nuclear Proteins / genetics*
  • Sequence Analysis, DNA
  • Transcription Factors / genetics*


  • ARID1A protein, human
  • ARID1B protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors

Associated data

  • GEO/GSE3960