April 5, 2011

Decoding DNA for Breast Cancer

(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