Neuroblastoma

Abstract

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.

The MYCN Protein in Health and Disease

“…It has very heterogeneous clinical presentations and prognosis [102]. According to the International Neuroblastoma Staging System (INSS), stages 1 to 3 include localized tumors, while stage 4 groups patients with metastases.…”

Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone

“…Overall, low-risk neuroblastomas mostly have whole chromosomal gains without structural aberrations. High-risk neuroblastomas, for example, mostly stage 4, on the contrary, present with different structural aberrations in the form of gains or losses of large chromosomal segments, referred to as segmental chromosomal aberrations (SCAs), MYCN amplification (MNA), and/or mutations as well as copy-number alterations affecting certain genes or parts thereof (5)(6)(7)(8)(9)(10)(11)(12)(13). Whether genetic markers might help to identify the relapse-seeding clone and to categorize stage 4 patients into different prognostic subgroups is still a matter of debate.…”

Neural crest and cancer: Divergent travelers on similar paths

“…Neuroblastoma is the most common type of cancer in the first year of human life and arises from the NC-derived sympathetic lineage (Matthay et al, 2016). During embryonic development, NC-derived sympathoadrenal progenitor cells migrate to the dorsal aorta, then undergo a secondary migration to form the sympathetic nervous system and chromaffin cells (Huber, 2006).…”