International team identifies 480 genes that control human cel...( PITTSBURGH A team of U.S. Israeli an...)

PITTSBURGH A team of U.S., Israeli and German scientists used computational biology techniques to discover 480 genes that play a role in human cell division and to identify more than 100 of those genes that have an abnormal pattern of activation in cancer cells.

Malignant cells have lost control of the replication process, so detecting differences in cell cycle gene activation in normal and malignant cells provides important clues about how cancers develop, said Ziv Bar-Joseph, a Carnegie Mellon University computational biologist who led the study. These genes also are potential targets for drug therapy.

Unlike many cancer studies, which seek to identify missing genes that might cause cancer, this new research shows that genes can contribute to cancer in less obvious ways. What we see is that there are many genes that are present and yet still involved in cancer because they are not activated, or expressed, in the way they normally are, said co-lead author Itamar Simon, a molecular biologist at Hebrew University Medical School in Israel. Rather than cycling on and off as normally occurs when cell replication and development proceeds, these genes are expressed in a steady state or not at all.

The findings will be reported in the online Early Edition of the Proceedings of the National Academy of Science during the week of Jan.7.

The genes found to be deregulated in cancer cells include a few, such as PER2 and HOXA9 that already have been linked to cancer. Most have not, including at least three genes responsible for repairing genetic mutations that occur as DNA is duplicated in the cell.

The failure of the DNA repair genes to cycle in cancer cells raises the possibility that some mutations associated with cancer may not cause cancer. Some of the mutations may be caused by the non-cycling genes, rather than the other way around, said Bar-Joseph, an assistant professor of computer science and machine learning in the School of Computer Sci
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