Childhood tumors that occur synchronously in different anatomical sites usually
represent metastatic disease. However, such tumors can be independent neoplasms. We investigated whether cases of bilateral neuroblastoma represented
independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood. Our results suggested that in both children, the lineages that had given rise to the tumors had
segregated within the first cell divisions of the zygote, without being preceded by
a common premalignant clone. In one patient, the tumors had parallel evolution,
including distinct second hits in SMARCA4, a putative predisposition gene for neuroblastoma. These findings portray cases of bilateral neuroblastoma as having
independent lesions mediated by a germline predispositio