Title:Biological and Genetic Features of Neuroblastoma and Their Clinical Importance
Volume: 14
Issue: 2
Author(s): Nevim Aygun*
Affiliation:
- Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir,Turkey
Keywords:
Neuroblastoma, biological and genetic features, clinical importance, genomic signature, chromosomal
abnormalities, cell signalling pathways, cell behaviour, clinical behaviour.
Abstract: Neuroblastoma derived from primitive cells of the sympathetic nervous system typically
develops in the adrenal medulla or paraspinal ganglia. Neuroblastoma usually occurs sporadically,
but familial cases are also observed. ALK and PHOX2B germline mutations can cause hereditary
neuroblastoma, while a common genetic variation in chromosome 6p22 is associated to sporadic
neuroblastoma. However, the aetiology of sporadic neuroblastoma is not exactly known. This
embryonic malignancy generally represents the second most common solid tumour after central
nervous system tumours throughout the world in childhood. Neuroblastoma is a complex disease that
has different clinical courses, from metastatic spread to spontaneous regression. Spontaneous
regression can occur without therapy in primary or metastatic site. Potential regression mechanisms
primarily involve apoptosis, hypermethylation of subtelomeric DNA, immune response and Nerve
Growth Factor (NGF) deprivation. Neuroblastoma is a heterogeneous tumour that can show many
different chromosomal abnormalities; e.g. MYCN amplification, 1p deletion, unbalanced
translocations involving chromosome 17, aneuploidies and Loss of Heterozygosity (LOH) events.
Tyrosine kinase receptors TrkA, TrkB and TrkC, their ligands NGF, Brain-derived Neurotrophic
Factor (BDNF) and Neurotrophin-3 (NT-3), and Aurora Kinase A (AURKA) play a regulatory role
in differentiation, apoptosis, cell proliferation, tumourigenesis, angiogenesis or metastasis of
neuroblastoma. TrkA expression is associated with differentiation or regression, depending on
presence or absence of NGF, whereas TrkB and BDNF are mostly expressed in aggressive
neuroblastomas with MYCN amplification. MYCN is amplified in 18-38% of neuroblastoma cases.
MYCN amplification mechanism remains to be completely clarified. This paper reviews the
biological/genetic features and their clinical importance in neuroblastoma.
