The expression profile of alternatively spliced neuronal c‐src RNA distinguishes between human tumours of the sympatho‐adrenal lineage

Human neuronal and neuroendocrine tumour specimens and cell lines were analysed regarding proteins and transcripts coded by the proto‐oncogene c‐src. At the protein level, most of the neuroblastomas and phaeochromocytomas expressed the neuronal c‐src form, pp60 c‐srcN . None of the other neuroendocrine tumours, i.e . paragangliomas, neuroendocrine pancreatic tumours, or carcinoid tumours and small‐cell lung carcinomas of different types, appeared to express the neuronal form. In the brain, c‐src is transcribed into 3 differently spliced mRNA variants, c‐src, c‐srcNI, and c‐srcNI + Nll. The expression of these transcripts was analysed by PCR amplification of fragments covering the mini‐exons Nl and Nll of the corresponding cDNAs. The PCR products were analysed by Southern hybridization and characterized by determination of their sequences. Neuroblastomas, paragangliomas, retinoblastomas and the phaeochromocytomas expressed neuronal c‐src splice variants. However, whereas neuroblastomas and retinoblastomas contained all 3 transcripts, the phaeochromocytomas and paragangliomas expressed, with 2 exceptions, only the c‐src and the c‐srcNI + Nll mRNA species. To assess whether neuroblastomas display adrenal chromaffin characteristics, they were analysed regarding expression of the chromaffin marker enzyme, phenylethanolamine‐N‐methyl transferase. Whereas phaeochromocytomas were positive, all neuroblastomas were immunochemically negative for this enzyme. These results and the c‐src expression profile suggest that neuroblastomas, including those with an adrenal location, do not originate from the adrenal chromaffin differentiation lineage. The data further suggest neuronal c‐srcNI mRNA as a marker for sympathetic neuronal cells of the sympatho‐adrenal lineage. © 1995 Wiley‐Liss, Inc.