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Use of microgenomic technology for analysis of alterations in DNA copy number and gene expression in malignant
J M Trent1, M Bittner, J Zhang
1Laboratory of Cancer Genetics, National Center for Human Genome Research, National Institutes of Health, Bethesda, MD 20892-4470, USA.
Abstract:
Chromosome abnormalities in human malignancies have identified the genomic location of several important growth-regulatory genes, including cellular oncogenes and tumour suppressor genes. Melanomas are characterized by recurring chromosome alterations, and it is important to identify those genes whose altered expression may be causally related to melanocytic transformation. This short report presents an overview of strategies used which combine the materials and technologies of the Human Genome Project with clinically directed studies of melanoma biology. The Human Genome Project combines various technologies, including cytogenetic, physical mapping, genetic mapping and DNA sequencing, in order to identify all of the human genes, but especially the 4000 estimated to contribute to human disease. This report focuses first on advances in genome technology that provide information on chromosome rearrangements and DNA copy number changes. This includes a discussion of chromosome microdissection as well as the microexcision of tissue specimens to gain insights into chromosome regions altered in association with melanocyte transformation. Next, there is a brief discussion of the generation and characterization of subtracted cDNA sublibraries which allow the identification of genes uniquely expressed in association with the transformed phenotype of human melanoma cells. Finally, we briefly discuss the feasibility of using a recently developed system for parallel examination of multiple genes based upon robotic printing of cDNAs on glass slides, and simultaneous two-colour fluorescence hybridization to study the expression patterns of cDNAs for their association with melanoma tumour suppression. The combination of these varied molecular technologies may provide insights into previously unrecognized genes involved causally in the pathobiology of this important neoplasm, and may provide new targets for clinical intervention.
Insights
Researchers are using Human Genome Project technologies to study melanoma, identifying genes involved in cancer development. This approach combines genomic analysis with clinical studies to find new therapeutic targets for melanoma.
Area of Science:
- Genomics and Cancer Biology
- Molecular Oncology
Background:
- Chromosome abnormalities are key in human cancers, including melanoma.
- Identifying genes driving melanoma transformation is crucial for understanding and treating the disease.
Purpose of the Study:
- To review strategies combining Human Genome Project technologies with melanoma studies.
- To identify genes causally related to melanocytic transformation and melanoma pathobiology.
Main Methods:
- Utilizing advances in genome technology for chromosome rearrangements and copy number changes.
- Employing chromosome microdissection and microexcision for altered regions.
- Generating and characterizing subtracted cDNA libraries for unique gene expression.
- Exploring parallel gene examination systems for expression pattern analysis.
Main Results:
- Genome technologies offer insights into chromosome alterations in melanoma.
- Subtracted cDNA libraries can identify genes associated with the transformed melanoma phenotype.
- High-throughput gene expression analysis can reveal associations with melanoma tumor suppression.
Conclusions:
- Integrating diverse molecular technologies provides a powerful approach to discover novel genes in melanoma.
- These findings may reveal new targets for clinical intervention in melanoma treatment.