Abstract: Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. 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 to determine the genetic basis for neuroblastoma. On average, each tumor had 19 somatic alterations in coding genes (range, 3-70). Chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 neuroblastomas (11%), and these were associated with early treatment failure and decreased survival. These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients.