Media Contact: Sandra Van[email protected]Tel. 1-800-396-1002
LOS ANGELES (Feb. 27, 2001) -- Using technology that enables them to analyze 18,000 genes in a single experiment, researchers at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute have identified four genes that may play a role in the development of certain types of malignant brain tumors.
The research, reported in the February issue of the International Journal of Oncology, may facilitate earlier detection of "glial" tumors and eventually allow scientists to devise new approaches to preventing and treating these often-devastating cancers.
Gene array techniques were developed in recent years by scientists racing to map the human genome. Although the costs are high, these studies allow thousands of genes to be analyzed quickly -- a much more efficient process than the previous method of looking at each gene individually. Now gene array methods are used nationwide to perform research in a variety of fields. Cedars-Sinai's Maxine Dunitz Neurosurgical Institute is one of a relatively few sites that have adopted this technology specifically for the purpose of finding genes that are implicated in brain cancer.
Research Scientist Julia Y. Ljubimova, M.D., Ph.D., the paper's first author, said gene-array technology has enabled Institute scientists to find several genes that are differentially expressed not only in glial tumors themselves but also in adjacent tissues that appear normal when viewed microscopically.
"When surgeons remove a malignant tumor, the adjacent tissue looks normal at the pathological level but it is the source from which a recurrence develops. Now, with the gene profile and the ability to view that tissue at the molecular level, it looks malignant," said Dr. Ljubimova. "This had previously been theorized but gene array technology allowed us to discover that fact."
According to Dr. Ljubimova (pronounced Lou-bee-mo-va), as new genes are discovered they contribute to a profile that can be used to monitor tumors, plan appropriate treatment, predict outcome and foresee recurrences. Furthermore, newfound genes will be used in the creation of custom-made "chips" -- the membranes made of nylon or other material containing the genes arrayed for analysis.
"Within the next few years, the genes responsible for glial tumors and other brain cancers will be identified. At that time, a chip specific to glial brain tumors may consist of 100 or 200 genes -- maybe more, maybe less -- but that chip will be specific to the diagnosis of glial tumors. The same situation will exist for breast cancer, prostate cancer and other diseases," said Dr. Ljubimova.
She anticipates that within the next decade the diagnosis of diseases -- including cancer -- will move to the molecular level on a routine basis, becoming as common as a blood profile is now. "Today we have about 100 parameters in a blood profile. In five or 10 years, because of gene and protein array technology, I believe we will have 100,000 parameters that will be used to diagnose tumors and all other diseases."
The ability to assess individual patients' genetic composition will unlock secrets that now baffle scientists and clinicians. "To use a very simple example, currently we may have two patients with the same histological type of tumor. Survival time for one patient is one year while survival time for the other patient is five years, and we don't know why," explained Dr. Ljubimova. "But in the future, gene diagnostics will make it easy to predict, to follow and to plan better treatments for patients."
The study published in the International Journal of Oncology looked specifically at cancers affecting glial cells. This study was designed to identify genes that expressed differentially in GBM, oligodendroglioma, and healthy tissue located adjacent to these tumors. By analyzing the characteristics exhibited by genes in these various tissues, the scientists hoped to find those that might be involved in the progression of normal glial cells to malignant cells.
As a result of their study, the team for the first time documented four genes that express differently in GBM and oligodendroglioma, compared to normal brain tissue. Two of the four are "known" genes -- their structures have been decoded or "sequenced." The other two are expressed sequence tags (ESTs) -- genes that are "unknown," having been identified but not yet sequenced in full.
According to Dr. Ljubimova, who has been involved in cancer research for about 17 years, identifying genes that appear to be involved in the mysterious multi-step process that transforms normal cells into malignant cells is merely the first part of years of research. Next, scientists will attempt to break down the genetic code of the "unknown" genes then they will characterize the genes, determining what they do in tumors versus normal tissue.
"Our goal is to find which genes are expressed exclusively in tumors so that we can eventually devise new strategies to block those genes and prevent tumor growth," said Dr. Ljubimova, who joined the Institute in mid-1998 to help establish its molecular biology laboratory.
Founded in 1997 by neurosurgeon and scientist Keith L. Black, M.D., the Maxine Dunitz Neurosurgical Institute has been credited with several previous gene discoveries.
In 1998, for instance, Dr. Black, Dr. Ljubimova and their colleagues discovered a gene -- malignancy-associated gene or MAG -- that exists in malignant tumors of the brain, liver, breast, colon, kidney and reproductive organs, but not in healthy adults. In 1999 they announced the discovery of 13 genes that are differentially expressed in brain tumors compared to normal tissue.
Dr. Ljubimova came to Cedars-Sinai in 1993 after performing cancer and other medical research in Kiev, Ukraine, at the Baylor College of Medicine in Houston, and at the University of California, San Diego. She received her medical degree from Kiev State University in Ukraine, and took advanced studies at the Kavetsky Institute for Oncology Problems at the Academy of Sciences of Ukraine and Moscow State University. She also earned her Ph.D. in oncology/pathology from the Kavetsky Institute.
The research in this study was performed entirely by scientists at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute, which also assumed all funding. A research scientist from Incyte Genomics, Inc., the developer of the Gene Discovery Array, also participated.
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For media information and interviews, please contact Sandra Van via e-mail at [email protected] or by calling 1-800-396-1002. Thank you.
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