Neuroblastoma, the third most common childhood tumour, originates from the sympathetic nervous system. Neuroblastoma is well known for its diverse clinical behaviour, ranging from spontaneous regression or maturation to aggressive metastatic disease. Neuroblastoma biology is complex and heterogeneous. The identification of genetic changes (
deoxyribonucleic acid
(DNA) ploidy,
MYCN
amplification and aberrations of chromosome 1p, 11q and 17q) and clinical variables (e.g. age and stage) that are highly predictive of outcome has facilitated stratification of patients into prognostic subsets and delivery of risk‐adapted therapies. However, the key events that govern neuroblastoma initiation, differentiation or progression remain elusive. To date, no single oncogene or tumour suppressor gene has been identified in the majority of neuroblastoma tumours. Furthermore, despite recent improvements with the addition of immunotherapy the survival for high‐risk neuroblastoma patients remains low and will require identification of novel therapeutic targets. The ultimate goal is to provide individualised assessment and therapy based on both the genetic variables of the patient as well as the tumour.
Key Concepts:
Neuroblastoma has diverse clinical behaviour and heterogeneous biology.
Amplification of the
MYCN
gene in neuroblastoma is prototypic for recurrent amplification of a proto‐oncogene in human cancers.
Both germline and somatic
ALK
mutations are present in neuroblastoma.
Specific genetic changes, such as MYCN amplification, or loss of heterozygosity of 1p or 11q are highly predictive of poor prognosis.
Neuroblastoma treatment involves risk‐adapted therapy, where patients are stratified into risk groups based on both clinical variables and tumour biology and the goal of current treatment strategies is to use these prognostic factors to decrease the intensity of therapy delivered to low and intermediate risk patients.
The current International Neuroblastoma Risk Group (INRG) Staging System utilises age, disease stage, tumour histology,
MYCN
status, DNA ploidy, aberrations of chromosome 11p to assign pre‐treatment risk groups.
DNA copy number alterations of primary tumours allow the identification of two subgroups: (1) whole chromosome gains that result in hyperdiploidy are usually present in favourable prognosis tumours and (2) segmental chromosomal aberrations (e.g. MYCN amplification) are usually associated with poor prognosis tumours.
Immunotherapy with anti‐GD2 antibody and cytokines following stem cell transplant has led to the first major improvement in survival for patients with high‐risk neuroblastoma in the past two decades.