Reuters Health Information (2004-10-01): Gene map illustrates multiple cancers' common genetic aberrations
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
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
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
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.