How can genomics be used to detect cancer?
A definitive diagnosis of cancer is largely based upon changes in cellular structure of tissue samples obtained by biopsy. Researchers have long recognized that cancer is due to changes in genes or gene activity, but difficulties in analytical methods have largely prevented taking advantage of this understanding until recently. The advent of the DNA microarray technology changed this situation, since it is now possible to rapidly analyze large numbers of genes in a patient's tissue sample. By using this technology, researchers have detected several genes that are related to specific cancers.
However, the detection of genes by itself does not reflect the dynamics of what is going on in the cell. Proteins are the functional units of the cell, and their formation, concentrations, and interaction with other molecules have direct influences on the development of cancer. Proteomics is concerned with the entire network of proteins in the cell or tissue. This is essential, since the progression of cancer is largely due to aberrant signaling pathways, or how the cell receives a stimulus for growth or other activities.
Cancer proteomics can be characterized into expression proteomics and functional genomics. 5 Expression proteomics seeks to identify proteins that are differently displayed in tissues that can be used as markers for cancer detection, diagnosis, and in the development of novel treatments. Functional proteomics, on the other hand, is related to how proteins interact with each other, with DNA and RNA, or as components of larger complexes. This approach recognizes that proteins are part of a dynamic system, and that just identifying individual proteins is not adequate to explain their function.
Laboratory techniques to analyze proteins
The application of proteomics to cancer detection is dependent on laboratory techniques that are rapid, accurate, and reasonably economical. Traditional protein separation and detection techniques have been based on chromatography and gel electrophoresis, which do not satisfy these criteria.
However, the advent of the microarray technology has revolutionized the field. Following-up on techniques developed for DNA technology, many companies have developed their own versions of protein microarrays or "protein chips." 2 The development of a protein chip is considerably more complex than its DNA counterpart, since proteins have a delicate three-dimensional structure that depends upon the physiological conditions in which they exist. Since protein function depends upon structure, the protein chips must maintain this structure. Protein microarrays are prepared by placing up to thousands of proteins as tiny spots onto a glass, metal or membrane surface. 1 Contrary to DNA fragments, proteins are quite variable in their physical properties, which make uniformity between spots difficult. A biological sample containing a mixture of proteins is then added to the "chip." Proteins in the mixture will bind to corresponding proteins on the chip. In order to detect the bound proteins, the chip proteins may be labeled by fluorescence or radioactive elements. In another detection method, the protein's molecular weight is determined by mass spectrometry.
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