Apr. 23, 1999 LOS ANGELES -- Using new technology that can analyze 18,000 to 20,000 genes at a time, researchers at the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center have found 13 genes that are differentially expressed in brain tumors compared to normal tissue.
Discovery of the genes is the first step in a process that may lead to more effective diagnosis, treatment or even prevention of brain tumors. Of the 13 new candidates, three are "known" genes -- their structures have been decoded or 'sequenced.' Ten others are 'expressed sequence tags' (ESTs) -- genes that are "unknown," having been identified but not yet sequenced in full. Whether the genes themselves are known or unknown, their functions within tumors are still a mystery.
"Our next step is to obtain the complete sequence of the unknown genes," according to Julia Y. Ljubimova, M.D., Ph.D., research scientist at the Institute. Breaking down a gene's code can take up to a year, she said, depending on the size of the gene. "Second, we have to characterize the genes. We must determine what they do in tumors versus normal tissue."
Dr. Ljubimova (pronounced "Lou-bee-mo-va"), who has been involved in cancer research for the past 15 years, said characterizing the genes -- understanding their activities and the results they produce -- may eventually unlock some of cancer's secrets, such as why tumor cells, unlike normal cells, grow without limit, or how they are able to invade other parts of the body.
"Our goal is to find which genes are expressed exclusively in tumors so that we can 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 lab.
The new gene identification method in use at the Maxine Dunitz Neurosurgical Institute, Gene Discovery Array, is one of the advances springing from the scientific community's race to map all of the genes of the human body. This type of "gene chip," robotics-based technology, is now being used by pharmaceutical companies to develop new drugs but is rarely found in clinical research settings.
"Gene Discovery Array is an extremely powerful tool," said Dr. Ljubimova. "Before, we could look at one, two or three genes at a time. Now, we are able to work with 18,000 to 20,000 genes -- to identify the differences in one panel in a rapid manner. It is providing very important data in medical oncology."
To confirm the validity of Gene Discovery Array findings, both qualitatively and quantitatively, the Neurosurgical Institute uses other state-of-the-art methods of molecular biology including reverse transcription-polymerase chain reaction and Northern blot analysis.
Whereas current studies seek to discover the genetic differences between malignant tissue and normal tissue, Dr. Ljubimova anticipates comparing tissue from different "grades" of tumors as well in the near future. Grade 2 tumors, for example, rarely metastasize while Grade 4 tumors often do. Comparing the genes expressed in each may provide clues into how cancer spreads. More importantly, it may result in treatments to keep cancer cells in check.
Under the direction of Keith L. Black, M.D., the Maxine Dunitz Neurosurgical Institute was launched at Cedars-Sinai Medical Center in 1997. Dr. Black, an internationally renowned neurosurgeon and scientist, co-authored with Dr. Ljubimova the preliminary findings that have been published in Proceedings of the American Association for Cancer Research and in neurosurgical journals.
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 Institute for Oncology Problems at the Academy of Sciences of Ukraine and Moscow State University. She earned her Ph.D. in oncology/pathology from the Kavetsky Institute for Oncology Problems at the Academy of Sciences of Ukraine.
Scientists at the Neurosurgical Institute and Cedars-Sinai were credited several months ago with the discovery of 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. Dr. Ljubimova was joined in that discovery by, among others, Dr. Black, director of the Institute; Dr. Achilles A. Demetriou, chairman of the Department of Surgery; and Dr. Stephen A. Geller, chairman of the Department of Pathology and Laboratory Medicine. Findings were reported in the October issue of Cancer Research, the journal of the American Association for Cancer Research.
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