Send to

Choose Destination
Nat Rev Dis Primers. 2016 Nov 10;2:16078. doi: 10.1038/nrdp.2016.78.


Author information

Department of Pediatrics and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94158, USA.
UCSF Benioff Children's Hospital, San Francisco, California, USA.
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
INSERM U830, SiRIC Laboratoire de Recherche Translationelle en Oncologie P├ędiatrique, and Department of Pediatric Oncology, Institut Curie, Paris, France.
Saga Medical Center Koseikan, Saga, Japan.
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
Departments of Neurology, Neurosurgery, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA.


Neuroblastoma is the most common extracranial solid tumour occurring in childhood and has a diverse clinical presentation and course depending on the tumour biology. Unique features of these neuroendocrine tumours are the early age of onset, the high frequency of metastatic disease at diagnosis and the tendency for spontaneous regression of tumours in infancy. The most malignant tumours have amplification of the MYCN oncogene (encoding a transcription factor), which is usually associated with poor survival, even in localized disease. Although transgenic mouse models have shown that MYCN overexpression can be a tumour-initiating factor, many other cooperating genes and tumour suppressor genes are still under investigation and might also have a role in tumour development. Segmental chromosome alterations are frequent in neuroblastoma and are associated with worse outcome. The rare familial neuroblastomas are usually associated with germline mutations in ALK, which is mutated in 10-15% of primary tumours, and provides a potential therapeutic target. Risk-stratified therapy has facilitated the reduction of therapy for children with low-risk and intermediate-risk disease. Advances in therapy for patients with high-risk disease include intensive induction chemotherapy and myeloablative chemotherapy, followed by the treatment of minimal residual disease using differentiation therapy and immunotherapy; these have improved 5-year overall survival to 50%. Currently, new approaches targeting the noradrenaline transporter, genetic pathways and the tumour microenvironment hold promise for further improvements in survival and long-term quality of life.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center