Oldridge DA, et al. - Considering the recently observed link between the primary tumor site, prognosis, and normally measured tumor biological features in neuroblastoma cases, researchers investigated whether neuroblastomas originating in different sites would demonstrate distinct genomic features indicative of the developmental biology of the sympathicoadrenal nervous system. They compared primary diagnostic neuroblastomas originating in the adrenal gland (N = 646) to thoracic sympathetic ganglia (N = 118) by analyzing genomic and epigenomic data. A total of 1,027 European-American neuroblastoma patients were examined to assess the association of common germline variation with these primary sites. Structural DNA aberrations, including MYCN amplification, were more likely to be exhibited by neuroblastomas arising in the adrenal gland, whereas hyperdiploidy resulting from defects in mitotic checkpoints was seen in thoracic tumors. Although a general association of ALK mutations with high-risk disease was observed, gain-of-function ALK aberrations were more likely to be seen in thoracic tumors. When malignant transformation occurred, the stage of sympathetic nervous system development was likely indicated by the site of origin, which was also identified as a surrogate for underlying tumor biology.