Amplified N-myc Gene as a Genetic Marker for the Prognosis of Human Neuroblastoma
Cytogenetic analyses have brought to light the frequency of DNA amplification in tumor cells and have provided a starting point to define the contribution for tumorigenesis that comes from an increase of the dosage of cellular oncogenes by amplification. Chromosomal abnormalities associated with DNA amplification are mainly of two types: double minutes (DMs), originally discovered in direct preparations of human neuroblastoma cells (Cox et al. 1965) and homogeneously staining chromosomal regions (HSRs), again detected in neuroblastoma cells (Biedler and Spengler 1976). In metaphase spreads, DMs appear as small, spherical, usually paired, chromosome-like structures that lack a centromere and may contain circular DNA in chromatin form. HSRs stain with intermediate intensity throughout their length rather than with the normal pattern of alternating dark and light bands in trypsin-Giemsa-stained preparations. Both kinds of abnormalities contain amplified DNA and are found in metaphases of freshly isolated cancer cells, but not of normal cells (Barker 1982). Exact data about the frequency of DMs and HSRs in tumor cells in vivo are difficult to obtain since the abnormalities are easily missed in routine cytogenetic analysis. DMs and HSRs have been described in most types of in vitro cultured malignant cells.
KeywordsHuman Neuroblastoma Cell Double Minute Cellular Oncogene Oncogene Amplification Proviral Insertion
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