Study finds genes that turn abnormal
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Most genes, like many people, work at scheduled times each day to complete assigned tasks. For genes, the goal is to keep cells functioning properly.
But what happens when certain genes go berserk -- begin working round the clock, at the wrong time or not at all? In those cases, cells can begin replicating themselves nonstop.
And the result can be cancer.
A study led by Carnegie Mellon University has detailed, for the first time, what genes likely are involved in that abnormal process. The findings are scheduled to appear this week on the online Early Edition of the Proceedings of the National Academy of Science.
CMU computational biologist Ziv Bar-Joseph, with assistance from German and Israeli researchers, developed a computer cell-replication model to identify genes involved in normal cell division and 118 candidate genes that show abnormal patterns of activation in cancer cells.
Study co-author Itamar Simon, a biologist at the Hadassah Medical School at Hebrew University in Jerusalem, said the identified genes "seem to be important."
"But we don't yet know which ones play key roles or might be targets for drug therapy," said Dr. Simon, who performed the biological experiments for the study.
Dr. Bar-Joseph, co-author, said he hopes the computational process eventually can be used to define the role of each gene and what combination of genes actually causes cancer-cell replication.
Once those genes are identified, medicines possibly can be developed to prevent their abnormal transformation.
A cancer specialist not involved with the research project said the study represents an important early step in understanding what genes are involved in cancer.
"This methodology will be able to be applied to many questions in cancer and in other disease fields," said Dr. Richard Steinman, associate professor at the University of Pittsburgh School of Medicine. "I think this paper is likely to have an important impact for scientists.
"The best thing you can do in a paper is help people ask better questions, and that is what this will do."
Cancer involves a complex array of genetic processes. But a key one causes cancer cells to replicate endlessly, resulting in tumors and metastasis. Previous studies had pinpointed only a few of those genes.
Dr. Bar-Joseph said there are roughly 25,000 genes in humans. With different genes becoming active at different times, trying to figure what genes are involved in cell division became a difficult scientific puzzle that CMU finally solved.
Researchers used a computer model to synchronize each step of the cell "cycle" -- the process a cell goes through to replicate itself. The model determined what genes were active in replication of normal cells but not active in cancer cells. The model also showed what genes were missing or behaving abnormally in cancer cells.
Besides identifying the candidate genes, the CMU study also showed that genes contribute to cancer in less obvious ways than previously thought.
"It's now clear that cancer is a multi-gene disease, and a number of things go wrong," Dr. Bar-Joseph said.
The eventual goal will be to produce a model of how human cancer occurs, then determine how to stop the process. With the study results, researchers also can begin testing how each identified gene functions in cells.
"We think the majority of genes we identified are right," Dr. Bar-Joseph said, noting the ultimate goal of identifying what genes actually cause cancer. "We believe this will give a big push in research in that direction."
First Published January 10, 2008 12:00 am