How Early Can We Detect Ovarian Cancer? January 2005

Scientists at the University of Minnesota have discovered 40 new genes associated with ovarian cancer, which could lead to the first screening test for the disease, something that has eluded scientists for decades. Although 90 percent curable when detected early, ovarian cancer is dubbed the "silent killer" because most women do not develop symptoms until the disease reaches an advanced stage. Without reliable early-detection methods, the "silent killer" has grown to be the fifth leading cause of cancer deaths for women in the United States. The well-known CA-125 test is useful for tracking patients already diagnosed with ovarian cancer, but has not proven sensitive enough to be used as an early diagnosis test. Scientists hope to develop an early-detection test that looks for genes expressed in ovarian cancer, but not in normal cells. Before that's possible, doctors first have to find out which genes need to be tested. In the August 2004 issue of the American Journal of Pathology, Dr. Amy Skubitz and colleagues at the University of Minnesota reported using GeneChip® microarrays to identify genes expressed in ovarian cancer. Skubitz' research group compared gene expression from 37 ovarian carcinoma samples to 50 normal ovarian tissue samples-far greater numbers than scientists had typically studied before. The researchers found over 4,000 genes that were expressed differently in the ovarian cancer samples. Of the 4,000 genes, the researchers figured that the best candidates for an ovarian cancer would be those genes that were not expressed anywhere else in the body. By comparing ovarian cancer gene expression to more than 300 other tissue samples from 24 different sites, such as kidney, breast, or lung, the scientists found 40 genes that were specifically expressed in ovarian cancer—not anywhere else. "By examining a large number of other types of tissues, we could identify genes relatively specific to ovarian carcinoma without relying entirely on the gene expression profile of normal ovary epithelial cells," said Skubitz. "A key step in determining the diagnostic potential of gene expression profiling is to compare the gene expression of a variety of tumors derived from many different organs." Using Affymetrix GeneChip® Human Genome U95 Arrays, Skubitz and colleagues were able to look at the expression level for each of the roughly 30,000 human genes in over 400 tissue samples. This throughput enabled researchers to identify a large number of new genes, including many with no previously known role in ovarian cancer. Previously, investigators studied one single gene at a time, an inefficient and time-consuming process — this also limited researchers to genes that were suspected to be involved with the development of ovarian cancer, missing the thousands of other genes that Skubitz' team identified as possible targets for future diagnostics or therapeutics. Uncovering a set of ovarian cancer "marker" genes is the critical first step toward the development of a much-needed early-detection test. While a microarray might be used as a diagnostic to detect expression levels for these genes, Skubitz and her team also found that some of the genes produce proteins that are secreted into the bloodstream, raising the possibility for a protein-based blood test as well. After decades of mystery, new early diagnosis tests finally promise to give the "silent killer" a voice that can be heard before it's too late. The Affymetrix GeneChip® Human Genome U95 Array is for research use only. References: (1) Hibbs, K, et. al. Differential Gene Expression in Ovarian Carcinoma - Identification of Potential Biomarkers. American Journal of Pathology. 165(2):397-414 (2004)