Decoding DNA for Breast Cancer
Reported April 5, 2011
(Ivanhoe Newswire) -- Scientists have sequenced the entire
genomes of tumors from 50 breast cancer patients and compared them to the
matched DNA of the same patients’ healthy cells. This was the single largest
cancer genomics investigation reported to date where comparison allowed
researchers to find mutations that only occurred in the cancer cells.
They uncovered incredible complexity in the cancer genomes but also got a
glimpse of new routes toward personalized medicine. In all, the tumors had more
than 1,700 mutations, most of which were unique to the individual.
"Cancer genomes are extraordinarily complicated," Matthew J. Ellis, M.D., Ph.D.,
professor of medicine at Washington University School of Medicine in St. Louis,
and a lead investigator on the project, was quoted as saying. "This explains our
difficulty in predicting outcomes and finding new treatments."
To undertake the massive task, Washington University oncologists and
pathologists at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and
Washington University School of Medicine collaborated with the university's
Genome Institute to sequence more than 10 trillion chemical bases of DNA --
repeating the sequencing of each patient's tumor and healthy DNA about 30 times
to ensure accurate data.
Ellis and colleagues found that two mutations were relatively common in many of
the patients' cancers. One called PIK3CA is present in about 40 percent of
breast cancers that express receptors for estrogen. Another called TP53 is
present in about 20 percent. In addition, they found a third mutation, MAP3K1,
which controls programmed cell death and is disabled in about 10 percent of
estrogen-receptor-positive breast cancers. The mutated gene allows cells that
should die to continue living.
"To get through this experiment and find only three additional gene mutations at
the 10 percent recurrence level was a bit of a shock," Ellis says. "We get good
therapeutic ideas from the genomic information … The near-term goal is to use
information on whole genome sequencing to guide a personalized approach to the
patient's treatment."
Ellis looks to future work to help make sense of breast cancer's complexity.
However, these highly-detailed genome maps are an important first step.
"At least we're reaching the limits of the complexity of the problem," Ellis
said. "It's not like looking into a telescope and wondering how far the universe
goes. Ultimately, the universe of breast cancer is restricted by the size of the
human genome."
SOURCE: American Association for Cancer Research 102nd Annual Meeting held in
Orlando, FL from April 2-6, 2011
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