To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Major Gene for Fatal Brain Cancer Discovered URL: http://www.pslgroup.com/dg/22876.htm Doctor's Guide March 27, 1997
SALT LAKE CITY, March 27, 1997 -- Researchers at Myriad Genetics, Inc. and The University of Texas M. D. Anderson Cancer Center in Houston have discovered a gene involved in the progression of brain tumors to glioblastoma multiforme (GBM), a fatal brain cancer affecting both adults and children. The gene was also found to be associated with some advanced cancers of the prostate, breast, kidney and skin. The identification of the gene MMAC1 (Mutated Multiple Advanced Cancers) reported in the April 1997 issue of Nature Genetics, provides new insights into cancer and is expected to accelerate efforts to find new treatments. "This brain cancer is very aggressive, and our research suggests that mutations in the MMAC1 gene play a role in advancing the aggressiveness of the tumor," said Peter Steck, Ph.D. associate professor of neuro-oncology at M. D. Anderson and the study's lead author. "The discovery will extend our understanding of this process not only in GBM, but also in several other solid tumors such as prostate, breast, kidney and skin." According to Dr. Steck, alterations to the gene have predominately been found in advanced forms of these cancers suggesting the gene may play a role in the malignant progression of certain cancers. Dr. Steck cautioned that while identification of the gene is an exciting laboratory research step, much more work lies ahead before new treatment strategies emerge for patients. "The sequence of the MMAC1 gene provides a number of important clues to its function, a key step in the search for drug targets and eventually for new treatments," said Sean Tavtigian, Ph.D., Director of Cancer Research at Myriad, the study's senior author. "The predicted function for MMAC1 as a key regulatory enzyme is very amenable to drug intervention. Through our collaboration with M. D. Anderson, we have already begun a directed research effort based on these findings to identify potential drug targets." An estimated 19,000 new cases of primary malignant brain tumors are expected to be diagnosed in the United States in 1997. These tumors are almost invariably fatal due to their location in the brain and infiltration into surrounding tissue. Primary brain tumors are the most common solid cancer in children and a leading cause of cancer deaths among individuals under the age of 15. These tumors are also the third most common cause of cancer death among patients 18 to 35 years old. The researchers localized the MMAC1 gene from tumor samples obtained from patients. From the samples, the researchers initially found large areas on chromosome 10 that were deleted. The researchers then narrowed their search to smaller areas, where both copies of the genetic material on chromosome 10 harbored deletions, and subsequently identified fragments of the gene. From these fragments, the researchers were able to determine the sequence of the entire gene and demonstrate that it was mutated both in tumor cell lines and in primary tumors. The researchers found the link to disease progression by comparing lower grade brain tumors to the more advanced glioblastomas. The area containing the MMAC1 gene was shown to be deleted in 36 of 37 samples on one of the two copies of chromosome 10 examined. Further analysis of six of these tumors uniformly revealed mutations in the MMAC1 gene on the other copy of chromosome 10. In contrast, while 4 of 12 lower grade brain tumors exhibited similar deletions, none of them had mutations in the gene. Analysis of DNA from other tumor types indicates that MMAC1 is mutated in other cancers, including, melanomas, and prostate, breast and kidney cancer. One interesting aspect of the MMAC1 gene for future therapeutic discovery is that the gene sequence suggests that it contains a segment encoding an enzyme that is part of a family of proteins called tyrosine phosphatases. These regulatory enzymes function to remove phosphate groups from proteins and act in tandem with specific enzymes, called tyrosine kinases, that add phosphates. "Blocking the activity of MMAC1's kinase counterpart, which is likely to be an oncogene, may represent a promising therapeutic strategy," said Dr. Tavitigian. "Our research has already identified candidate proteins that interact with MMAC1 with the aim at identifying the specific tyrosine kinases and associated phosphorylation substrates that act along the MMAC1 pathway." The paper is being published under the title: "Identification of a Candidate Tumor Suppressor Gene at 10q23.3 that is Mutated in Multiple Advanced Cancers." The gene had initially been named BNC1 based its role in brain cancer. The collaborators renamed the gene MMAC1 following research linking it to other high grade cancers. A portion of the research was supported by the National Institutes of Health, the Pediatric Brain Tumor Foundation, the Gilland Foundation and the American Brain Tumor Association. Myriad Genetics, Inc., is a gene discovery and genetic testing company focused on the discovery and commercialization of genes involved in major common disorders, including cancer, cardiovascular disease and central nervous system disorders. The Company is involved in strategic alliances with Novartis Pharmaceuticals Corp., Bayer Corp., and Eli Lilly and Co. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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