Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma.

TLDR

DNA similar to N‑myc is frequently amplified in human neuroblastoma cell lines and tumors. The study hypothesizes that N‑myc amplification and overexpression drive malignant progression in neuroblastoma. N‑myc amplification is tumor‑specific, with a 4‑kb mRNA highly expressed in neuroblastoma and retinoblastoma cells, absent in other tumor lines and normal fibroblasts, and up to 80‑fold higher in amplified lines, especially in undifferentiated neuroblasts.

Abstract

Previous studies had revealed that DNA with partial similarity to the myc oncogene (N-myc) is frequently amplified in human neuroblastoma cell lines and neuroblastoma tumors. We show here for one patient that N-myc amplification is confined to the neuroblastoma tumor and is not present in normal tissue. N-myc mRNA approximately equal to 4.0 kilobases in size is detectable in neuroblastoma cell lines and tumors and in a retinoblastoma cell line. By contrast, appreciable amounts of this RNA were not present in a number of cell lines derived from other human tumors and in fibroblasts from a normal individual and from a neuroblastoma patient. Low levels of N-myc RNA were found in human and murine neuroblastoma cell lines lacking amplification of this gene, up to 80-fold greater levels in all cell lines carrying amplified N-myc. In situ hybridization to sections of neuroblastoma tumors revealed high expression of N-myc predominantly in undifferentiated neuroblasts. We hypothesize that amplification and consequent elevated expression of N-myc may be related to malignant progression.