Science

Gene map illustrates multiple cancers' common genetic aberrations

Last Updated: 2004-10-01 14:45:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Tumors can be characterized by combinations of a relatively small number of gene sets, called modules, that act in concert to carry out specific functions, a research team reports in the journal Nature Genetics, published online September 26. Often, the same modules are involved in a wide variety of clinical conditions.

Characterizing these modules will help "bridge the gap between microarray analysis and the clinic," senior author Dr. Aviv Regev told Reuters Health. "It will benefit cancer genomic researchers by helping identify genes that could serve as new targets for cancer diagnosis or therapeutics."

Dr. Regev, at Harvard University in Cambridge, Massachusetts, and her colleagues started by analyzing a compendium of nearly 2000 DNA microarrays representing 22 tumor types.

From this they identified "456 statistically significant modules that span various processes and functions, including metabolism, transcription, translation, degradation, cellular and neural signaling, growth, cell cycle, apoptosis and extracellular matrix and cytoskeleton components."

They could then define clinical conditions according to the combination of modules that are induced or repressed.

They next constructed a "global module map for cancer," which showed that some modules are specific to the particular types of tumors. For example, the authors explain, hematologic tumors involve similar immune, inflammation, growth regulation and signaling modules, where the specific patterns of involvement separate the different tumor types.

Other modules span a variety of tumor types, suggesting common tumor progression mechanisms. A case in point is the "bone osteoblastic module," which is associated with proliferation and differentiation of bone-building cells and plays a role in bone metastasis of cancers of the breast, lung and liver and leukemias.

Dr. Regev used the antileukemia drug Glivec/Gleevec to illustrate how the module map can be used: "Glivec's target is a well-known protein, so one can look at what happens to this protein. To which module does it belong? How does that module relate to many different kinds of cancer? That information in turn could suggest other cancers that might be a relevant target for this drug."

Their results are being made publicly available at http://dags.stanford.edu/cancer. There, scientists "can browse the genes or modules of interest, or whatever clinical condition they are researching," Dr. Regev said.

The team has also posted the software package they used, GeneXPress, at http://GeneXPress.stanford.edu. "This is a tool that is very fast, with a nice interface," that doesn't require the user to know how to program computers, Dr. Regev noted. Users "can then repeat this entire exercise on their own data sets."

Other collaborators on this project are Drs. Eran Segal and Daphne Koller at Stanford University in California and Dr. Nir Friedman at Hebrew University in Jerusalem.

Nat Genet 2004.