Heiko Hermeking PhD


Alterations in Oncogenes and Tumor Suppressor Genes

Cause Cancer Oncogenes as Anticancer Drug Targets

Techniques Used for Identification of Oncogenic Amplifications From SAGE to LongSAGE: Incorporating the Genomic Level Digital Karyotyping: Charting Cancer Cell Genomes Validation of Digital Karyotyping Results Further Applications of Digital Karyotyping in Cancer Research Alternatives to Digital Karyotyping References


Activated oncogenes are required for the initiation and maintenance of the cancer cell phenotype, and, therefore, represent attractive therapeutic targets. Specific inhibition of oncogene products was recently approved for cancer treatment. Oncogene activation often results from genomic amplification. The SAGE (serial analysis of gene expression) method has recently been adapted to the analysis of genomic alterations, including amplifications. As a first step in this direction, LongSAGE, which allows one to localize differentially expressed SAGE tags/mRNAs in the human genome, was devised. Subsequently, the LongSAGE protocol was adapted to the quantitative analysis of copy-number changes in genomic DNA. This new method, named Digital Karyo-typing, identifies amplifications at an unprecedented resolution. In this chapter the SAGE-based quantification of gene expression and genomic copy-number changes is described as well as how it might be integrated into the identification of oncogenes and cancer drug targets.

Key Words: Oncogene; cancer therapy; Digital Karyotyping; SAGE; serial analysis of gene expression; drug target; tumor biology; tumor suppressor gene; amplification.

From: Cancer Drug Discovery and Development: The Oncogenomics Handbook Edited by: W. J. LaRochelle and R. A. Shimkets © Humana Press Inc., Totowa, NJ

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