Cancer research explosion imminent

Abstract

In September 1999, Incyte Pharmaceuticals (Palo Alto, CA, USA) and the Huntsman Cancer Institute (HCI, University of Utah, UT, USA) announced a partnership that could provide a huge boost to our understanding of the molecular basis of cancer. For the next two years at least, Incyte will provide HCI with its LifeSeq Gold database of human genes (Box 1 and Fig. 1) and its system of microarray technology (Box 2) in return for the HCI’s cancer expertise. Box 1. Incyte’s LifeSeq Gold database LifeSeq Gold contains gene expression information for 895 tissue libraries, in both normal and diseased systems, and at different developmental stages. It currently contains 4.3 million expressed sequence tags (ESTs), 3.3 million of which are Incyte-proprietary. This represents more than 90% of all expressed human genes, 50 000 of which are not available in the public domain. Scott predicts that, with the completion of the human genome project in April 2000, ‘expansion of the database to contain all expressed human genes will follow by the end of the year.’ Box 2. Gene expression microarray technology Each of Incyte’s microarrays is tailored to an individual biological system. A library of cDNA molecules containing the genetic information from cells within the chosen system is constructed and then individual cDNA molecules are isolated and amplified. A micro-sample of each cDNA is then deposited on a glass surface in an array format with each gene occupying a unique location. The micro-samples are bonded to the glass; 10 000 unique cDNAs can be assembled in a single array, each gene 500–5000 bp in length. When the array is used, large portions from one half of the DNA’s double strands are first removed. This process activates the individual elements of the array, preparing them to react and bind to their uniquely matched DNA counterparts in the test cells. In the colon cancer experiments at HCI, cells from different stages of tumour development will be compared to see which genes are expressed at which stage. mRNA extracted from a normal cell will be used to generate a fluorescence-labelled cDNA probe that will represent all of the genes expressed in a normal colonocyte. The process will be repeated for a cancerous cell, but using a differently coloured fluorescent marker. The two fluorescent probe samples will then be applied simultaneously to a single microarray, to react competitively with the arrayed cDNA molecules. By reading the pattern of fluorescence, researchers should be able to determine genes that are expressed in the cancerous cells, but not in normal cells. LifeSeq Gold contains gene expression information for 895 tissue libraries, in both normal and diseased systems, and at different developmental stages. It currently contains 4.3 million expressed sequence tags (ESTs), 3.3 million of which are Incyte-proprietary. This represents more than 90% of all expressed human genes, 50 000 of which are not available in the public domain. Scott predicts that, with the completion of the human genome project in April 2000, ‘expansion of the database to contain all expressed human genes will follow by the end of the year.’ Each of Incyte’s microarrays is tailored to an individual biological system. A library of cDNA molecules containing the genetic information from cells within the chosen system is constructed and then individual cDNA molecules are isolated and amplified. A micro-sample of each cDNA is then deposited on a glass surface in an array format with each gene occupying a unique location. The micro-samples are bonded to the glass; 10 000 unique cDNAs can be assembled in a single array, each gene 500–5000 bp in length. When the array is used, large portions from one half of the DNA’s double strands are first removed. This process activates the individual elements of the array, preparing them to react and bind to their uniquely matched DNA counterparts in the test cells. In the colon cancer experiments at HCI, cells from different stages of tumour development will be compared to see which genes are expressed at which stage. mRNA extracted from a normal cell will be used to generate a fluorescence-labelled cDNA probe that will represent all of the genes expressed in a normal colonocyte. The process will be repeated for a cancerous cell, but using a differently coloured fluorescent marker. The two fluorescent probe samples will then be applied simultaneously to a single microarray, to react competitively with the arrayed cDNA molecules. By reading the pattern of fluorescence, researchers should be able to determine genes that are expressed in the cancerous cells, but not in normal cells.