'Smothered' genes combine with mutations to yield poor outcome in cancer patientsJuly 16, 2008Johns Hopkins Kimmel Cancer Center researchers have identified a set of genes in breast and colon cancers with a deadly combination of traditional mutations and "smothered" gene activity that may result in poor outcomes for patients. The Hopkins team showed that this smothering process, called epigenetic inactivation, contributes to the aggressiveness of breast and colon cancer by disrupting biochemical pathways that normally suppress the runaway growth of cells that is the hallmark of cancer. While mutations alter pathways by rewriting the gene's DNA code, epigenetic marks affect genes without changing the code itself. "Until studies like ours, it was easy to think that if we didn't find gene mutations in certain biochemical pathways linked to breast or colon cancer, then those pathways were normal in such patients," says Stephen Baylin, M.D., the Virginia and D.K. Ludwig Professor for Cancer Research and deputy director of the Kimmel Cancer Center. "Now we know that, in some patients, the pathways involved with newly discovered mutated genes are often more frequently disrupted by epigenetic mechanisms rather than genetic ones."
"That's a powerful insight that could help us diagnose patients quicker, predict the course of their cancer more accurately and in the future treat the disease more effectively," adds Baylin. A report on this work appeared May 27 in PLoS Medicine. The team made their discovery using microarray technology - special silicon chips carrying pieces of genetic material that allow thousands of genes to be analyzed at one time. For this study, microarrays were tailored to locate cancer-related genes inactivated by an epigenetic process called DNA methylation. This methylation involves the binding of molecules called methyl groups to elements of DNA called cytosines that are located in a gene's "on-off switch." Excess methylation smothers the gene with too many methyl groups and interferes with the gene's normal protein production, setting the stage for a lethal cancer. Some 189 mutated genes in breast and colon cancers, previously identified by a Kimmel Cancer Center research team, were screened for methylation by Baylin's group. They found 36 genes that were infrequently mutated in cancer, but were "hyper"methylated, often in both breast and colon cancers. After reviewing samples from 30 breast and 20 colorectal cancer patients as well as information from public microarray databases, the researchers found 18 of these genes that were strongly linked to poor outcome of patients with tumors carrying these changes. For most of the genes, the researchers were able to reverse their epigenetic change and reactivate them in test tubes by stripping off excess methyl groups. This suggests that new treatments designed to reverse hypermethylation could be a simpler and more practical approach to treating cancer than strategies that attempt to replace, deactivate or compensate for mutated genes, according to Baylin. Baylin also believes that the methlylated genes identified in this study could be inactivated in a broader range of cancers as well. That means the current findings could be extended to other cancers, improving the ability of physicians to predict the course of additional types of tumors, he says. "We've learned from this study that we must include both genetic and epigenetic changes when we do future microarray analyses to increase our understanding of the genetic basis of cancer," Baylin says. "Such information will provide new details about why cancers start and help us identify which cancers will be particularly aggressive in our patients." Johns Hopkins Medical Institutions | |||||||||||||||||||||
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Related Colon Cancer Current Events and Colon Cancer News Articles Breakthrough optical technology to assess colon cancer risk, accuracy Researchers at NorthShore University HealthSystem (NorthShore) and Northwestern University have discovered that fiber optic technology can for the very first time effectively measure blood levels in the colonic lining (mucosa) in humans, thus having potential applications for analyzing risk of colon cancer. Surgical treatment provides new option for some colorectal cancer patients Research out of Wake Forest University School of Medicine suggests that a surgical technique not traditionally used in advanced abdominal cancer may be a viable treatment option for some patients previously thought to be untreatable, offering the real possibility of extending survival for those patients. Black Americans Are At Greater Risk for Colon Polyps Black Americans have a higher occurrence of colon polyps, according to a new study. This is a significant finding considering the incidence of colon cancer among black men has increased and remained unchanged among black women during the last 20 years. Cancer-causing gut bacteria exposed Normal gut bacteria are thought to be involved in colon cancer but the exact mechanisms have remained unknown. Now, scientists from the USA have discovered that a molecule produced by a common gut bacterium activates signalling pathways that are associated with cancer cells. Brown-Assisted Trial Finds New Colorectal Screening Procedure Is Accurate and Less Invasive More patients stand to benefit from a comprehensive, less invasive method to accurately detect colorectal cancer and precancerous polyps, a multicenter study involving Brown University and institutions nationwide has found. Researchers identify cancer-causing gene in many colon cancers Demonstrating that despite the large number of cancer-causing genes already identified, many more remain to be found, scientists at Dana-Farber Cancer Institute have linked a previously unsuspected gene, CDK8, to colon cancer. '1-hit' event provides new opportunity for colon cancer prevention, say Fox Chase researchers More than 30 years ago, Alfred Knudson Jr., M.D., Ph.D., revolutionized the field of cancer genetics by showing that a person must lose both their paternal and maternal copies of a particular class of cancer-inhibiting genes, called tumor-suppressor genes, in order to develop cancer. Early stage colon cancer characterized by inactivation of gatekeeper gene The absence or inactivation of the RUNX3 gatekeeper gene paves the way for the growth and development of colon cancer, Singapore scientists report in the Sept. issue of the journal Cancer Cell. Previous studies have shown that RUNX3 plays a role in gastric, breast, lung and bladder cancers. Variation of normal protein could be key to resistance to common cancer drug Researchers at the Moores Cancer Center at the University of California, San Diego (UC SD) in La Jolla have found evidence explaining why a common chemotherapy drug, cisplatin, may not always work for every cancer patient. They have shown that when a variant version of a key protein that normally causes cell death is active, patients may be resistant to the cancer-killing drug. Anti-Cancer Flower Power Could a substance from the jasmine flower hold the key to an effective new therapy to treat cancer? More Colon Cancer Current Events and Colon Cancer News Articles |
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