Neural crest development and neuroblastoma: the genetic and biological link

Abstract

Neuroblastoma is one of the most common pediatric solid tumors originating from the sympathoadrenal lineage of neural crest. The tumor shows extremely different clinical phenotypes such as spontaneous regression on one hand and aggressive growth on the other hand. The different biological behavior of neuroblastoma appears to be determined by the genetic abnormalities including amplification of MYCN oncogene, DNA ploidy and some allelic imbalances. However, the spontaneous regression of neuroblastoma mimics the programmed cell death normally occurring in developing sympathetic cells expressing both TrkA tyrosine kinase A and p75NTR neurotrophin receptor. Indeed, TrkA expression is the most important factor related to the induction of tumor cell differentiation and/or programmed cell death because without its expression spontaneous regression of neuroblastoma never occurs. Thus, the enigmatic clinical behaviors of neuroblastoma are strictly linked to the molecular mechanism of neural crest development.