Characterisation of stable cell clones derived from an unusual neuroblastoma stage 4S with MYCN amplification

Neuroblastoma (NB) is the most common extracranial solid tumour of childhood. One of its most remarkable biological properties is spontaneous regression in patients with tumour stage 4S despite disseminated disease. Major biological factors determining the outcome of NB are the status of the MYCN oncogene and differenzial expression of neurotrophin receptors of the Trk family. While expression of the TrkA receptor is associated with favourable outcome, expression of TrkB as well as MYCN amplification correlate with aggressive tumour characteristics and poor prognosis. Here, we report the molecular characterisation of an unusual stage 4S neuroblastoma with MYCN amplification and adverse outcome. Co-expression of both, TrkA and TrkB, was found in tumor cells as well as in primary cultures derived from this tumor in vitro. Several independent cell clones designated as NB4S-CC were obtained by limited dilution of tumour cells. Using CD56 immunostaining, all NB4S-CC were shown to be bona fide NB cells. Functional assays to characterise the response of the different NB4-CCs to neurotrophin receptor ligands as well as cytogenetic characterisation of these cells are underway. It remains to be determined, to what extent these cell clones can serve as model systems to understand the interaction of MYCN and TrkA/TrkB in NB.