• Tim H H Coorens, Sarah J Farndon, Thomas J Mitchell, Neha Jain, Sangjin Lee, Michael Hubank, Neil Sebire, John Anderson, and Sam Behjati.
• From the Wellcome Sanger Institute, Hinxton (T.H.H.C., T.J.M., S.L., S.B.), Cambridge University Hospitals NHS Foundation Trust (S.J.F., T.J.M., S.B.) and the Departments of Surgery (T.J.M.) and Paediatrics (S.B.), University of Cambridge, Cambridge, and UCL Great Ormond Street Institute of Child Health (N.J., N.S., J.A.), Great Ormond Street Hospital for Children NHS Foundation Trust (N.J., N.S., J.A.), and the Royal Marsden NHS Foundation Trust (M.H.), London - all in the United Kingdom.
• N. Engl. J. Med. 2020 Nov 5; 383 (19): 186018651860-1865.

AbstractChildhood 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 predisposition. (Funded by Children with Cancer UK and Wellcome.).Copyright © 2020 Massachusetts Medical Society.

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