Molecular and Biological Heterogeneity in Neuroblastoma

E.      Hiyama; K.      Hiyama

Abstract

Neuroblastoma, one of the common malignant childhood tumors, arises from neuroblast cells derived from the neural crest and destined for the adrenal medulla and the sympathetic nervous system and shows remarkable biological heterogeneity, resulting in favorable or unfavorable outcomes. Some neuroblastomas tend to regress spontaneously in infants or to differentiate into a benign ganglioneuroma in older patients. In other instances, the tumors make rapid progress with a fatal outcome. This heterogeneity within neuroblastoma depends on the molecular characteristics of tumor cells. Several distinct genomic alterations have been found in neuroblastoma, including MYCN amplification, ploidy changes, deletion of the short arm of chromosome 1, gain of chromosome 17q, and deletion of 11q. The difference of expression was also found in genes related to cellular growth, differentiation, and apoptosis of neural network including Trk receptor tyrosine kinase and telomerase activity. This review discusses the extensive heterogeneity of neuroblastoma at molecular level, providing evidences that neuroblastoma is not a single disease. This should lead to more risk-adapted therapies according to the genetic markers by which individual neuroblastomas are biologically characterized.

Keywords: neuroblastoma, prognosis, mycn, ploidy, chromosome, telomerase, telomere, apoptosis