Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour

Abstract

Amplified cellular genes in mammalian cells frequently manifest themselves as double minute chromosomes (DMs) and homogeneously staining regions of chromosomes (HSRs). With few exceptions both karyotypic abnormalities appear to be confined to tumour cells. All vertebrates possess a set of cellular genes homologous to the transforming genes of RNA tumour viruses, and there is circumstantial evidence that these cellular oncogenes are involved in tumorigenesis. We have recently shown that DMs and HSRs in cells of the mouse adrenocortical tumour Y1 and an HSR in the human colon carcinoma COLO320 contain amplified copies of the cellular oncogenes c-Ki-ras and c-myc, respectively. Both DMs and HSRs are found with remarkable frequency in cells of human neuroblastomas. We show here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification. By in situ hybridization we found that HSRs are the chromosomal sites of the amplified DNA. The frequency with which this amplification appears in cells from neuroblastomas and its apparent specificity raise the possibility that one or more of the genes contained within the amplified domain contribute to tumorigenesis.

Interferon-? cooperates with retinoic acid and phorbol ester to induce differentiation and growth inhibition of human neuroblastoma cells

“…1,2 A number of prognostic parameters for the disease have been identified, including age, loss of heterozygosity at chromosome 1p36, DNA ploidy, histopathologic stage and amplification of the N-myc proto-oncogene. [3][4][5][6][7][8] The latter condition is strongly correlated with advanced disease, insensitivity to chemotherapy and poor outcome. 9 -12 N-myc and other members of the myc family encode transcription factors that control the expression of genes involved in cell growth, differentiation and survival.…”

Expression of mRNA for the neurotrophin receptor trkC in neuroblastomas with favourable tumour stage and good prognosis

“…The clinical heterogeneity of NB has stimulated an intensive search for biological markers correlated with prognosis, in order to allow, at an early stage the assessment of the individual patient as having favourable or poor prognosis respectively. Genomic amplification of the N-myc oncogene (MYCN), is correlated with advanced stage and unfavourable outcome (Brodeur et al, 1984;Schwab et al, 1983;Seeger et al, 1985). Genetic aberrations found in NB include other structural chromosomal abnormalities, in particular deletions involving the short arm of chromosome 1 (Brodeur et al, 1977).…”

Characterization of a highly conserved gene (OS4) amplified with CDK4 in human sarcomas

“…After normalization relative to b-actin, expression of OS4 and CDK4 was estimated by densitometry to be more than tenfold higher in the cell lines, NGP-127, RMS-13, and OsA-Cl with ampli®cation of these two genes than the non-ampli®ed lines, U-2 OS and HOS, and the normal tissues, spleen, pancreas, and skeletal muscle. NGP-127: neuroblastoma (Schwab et al, 1983); RMS-13: rhabdomyosarcoma (Roberts et al, 1989; OsA-C1: osteosarcoma (Roberts et al, 1989); U-2 OS: osteosarcoma (Ponten and Saksela, 1967); HOS: osteosarcoma (Rhim et al, 1975) Placenta T1 T2 T3 T4 T5 9.4 -9.4 -6.6 -4.4 -…”

“…The human cancer cell lines, OsA-Cl (osteosarcoma) (Roberts et al, 1989), RMS-13 (rhabdomyosarcoma) (Roberts et al, 1989), NGP-127 (neuroblastoma) (Schwab et al, 1983), HOS (osteosarcoma) (Rhim et al, 1975) (Sambrook et al, 1989). Poly(A) + RNA was puri®ed using the FastTrack kit 2.0 (Invitrogen).…”