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'Smothered' genes combine with mutations to yield poor outcome in cancer patients

Johns 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 gro

Contact: Vanessa Wasta
Johns Hopkins Medical Institutions

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