Locating Novel Breast Cancer Genes using DNA Microarrays
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cancer results from the deregulated control of normal cell growth, and is caused by alterations in the cell's DNA sequence- its genetic code. These alterations can take the form of DNA sequence mutations, which are subtle alterations in the genetic code (e.g. Sickle cell anemia). But in cancer, especially advanced disease, these genetic alterations often take the form of duplicated (or triplicated, etc.) and deleted DNA sequences. The result is that too much or too little of a given gene is present, leading to the dramatic cellular changes seen in tumor cells. Cataloguing these gene copy number alterations, and identifying the specific genes involved, might lead to an improved understanding of cancer and point us towards developing improved therapeutic agents. For example, Herceptin is a therapeutic now used to treat breast cancers with excess Her-2/neu growth oncogene on the tumor cell surface. But, the use of Heceptin became most effective only after patients were directly evaluated for multiple copies of the gene using a microscopic assay, called FISH (fluorescence in situ hybridization).
 
 
 
 
 
 
 
 Our hypothesis is that chromosome regions (genes) of "extra" DNA sequence copy number are, (1) undiscovered by conventional, lower-resolution techniques, and (2) contain possible breast cancer genes that might be used as "markers" or therapy targets in treatment. We aim to test and develop this hypothesis by using a new technique, based on DNA microarrays. A DNA microarray consists of a glass microscope slide onto which thousands of different DNA sequences (genes) are placed in an ordered array of rows and columns. DNA microarrays were first used to measure the expression of genes, and this has proven to be a powerful method for classifying breast cancer into molecular subtypes. In this project we plan to extend this approach to map DNA sequence copy number. The advantage is that thousands of genes can be assayed simultaneously, and any identified gene can be immediately located using data from the Human Genome Project. We plan to use 25 human breast cancer cell lines and &gt;100 primary human tumor samples to obtain a database of genetic changes. We will "map" the genetic changes in these samples versus a standard human genome. While the data are accumulating we anticipate finding genes where amplifications or deletions are recurrent, and we will be able to differentiate these from non-informative DNA alterations (i.e., not associated with breast cancer). Finally, we plan to combine this novel approach of molecular genetics analysis with our growing database of gene expression. Taken together we will have a list of potential oncogenes (i.e., genes increased in cancer) and tumor suppressors (i.e., genes lost in cancer progression) for further study.
 
 
 
 
 
 
 
 In the past, gene copy number alterations have been mapped by examining chromosomes through a microscope. Such methods have provided comparatively low mapping resolution, which has slowed efforts to locate actual cancer genes. The proposed study takes advantage of an innovate DNA microarray technique to map DNA at unprecedented resolution, thereby speeding the process and making sense of the complex problem of cancer genetics.