BBB seminar: Karl-Henning Kalland
Global analysis of gene expression and regulatory patterns in cancers using DNA microarrays
Centre of Virology, Dept. of Microbiology and Immunology, The Gade Institute, University of Bergen
The DNA microarray technology is rapidly evolving. It is now possible to represent all human genes on one single glass slide, and achieve a corresponding distribution of signal intensities of a hybridized and fluorescently labeled mixed RNA sample. When two different RNA samples are labeled with two different and suitable fluorochromes, a direct comparison of gene expression levels of each gene is possible using one single DNA microarray slide. The sensitivity of the hybridization procedure is sufficient to detect very low abundance mRNA species. The resolution of the DNA microarray analysis is not limited by detection sensitivity, but instead by non-specific cross-hybridization.
Using mRNA extracted from malignant and benign prostate biopsies and from endometrial cancer biopsies and acute myeloid leukemia blasts, our project constellations have identified genes differentially expressed in cancer. Several sources of error and noise are still inherent in the microarray technology. Independent validation of gene expressions, using e.g. bioinformatic tools, statistics, real time quantitative PCR, immunohistochemistry and in situ hybridization, is therefore required. When properly designed and executed the DNA microarray technology is useful for the discovery of genes aberrantly regulated in cancer and for the identification of relevant regulatory gene modules. Gene expression patterns of prognostic and predictive value can also be revealed.