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Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc
Abstract:
Cellular oncogenes comprise a class of genes whose aberrant expression or function may be involved in the development of tumours. Indeed, several naturally occurring animal and human tumours are associated with consistent alterations in the structure or genomic position of particular cellular oncogenes. Recently, we isolated a DNA segment having limited similarity to c-myc (termed N-myc) from a human neuroblastoma cell line. Although N-myc was present as a single copy in normal cells, it was selectively amplified up to 140-fold in tumour cells from human neuroblastomas. Now, we have used somatic cell hybrids to show that N-myc is normally localized on the distal short arm of chromosome 2, and in situ hybridization to localize N-myc to chromosome 2p23-24. Further, in situ hybridization localizes amplified N-myc in neuroblastoma cells to homogeneously staining regions (HSRs) on different chromosomes. Thus, our results suggest that amplification and translocation of N-myc may be interrelated processes associated with human neuroblastoma, and demonstrate that the site of N-myc amplification is quite variable and bears no apparent relationship to either the normal single-copy locus or recognized sites of non-random chromosome alteration in human neuroblastoma.
Insights
Neuroblastoma tumors show amplified N-myc oncogene, which is normally on chromosome 2. Amplified N-myc is found in variable locations, suggesting its translocation is linked to tumor development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Aberrant oncogene expression is linked to tumor development.
- Specific oncogene alterations are observed in human tumors.
- N-myc, similar to c-myc, was identified in neuroblastoma cell lines.
Purpose of the Study:
- To determine the normal location of the N-myc gene.
- To investigate the genomic location of amplified N-myc in neuroblastoma.
- To explore the relationship between N-myc amplification and translocation in neuroblastoma.
Main Methods:
- Somatic cell hybridization to map the N-myc locus.
- In situ hybridization to pinpoint N-myc on chromosomes.
- Analysis of amplified N-myc in neuroblastoma cell lines.
Main Results:
- N-myc is normally located on chromosome 2p23-24.
- N-myc is amplified up to 140-fold in neuroblastoma tumor cells.
- Amplified N-myc is found in homogeneously staining regions (HSRs) on various chromosomes.
Conclusions:
- N-myc amplification and translocation may be interrelated in human neuroblastoma.
- The site of N-myc amplification in neuroblastoma is variable.
- Amplification sites lack apparent relation to the normal N-myc locus or known alteration sites.