Scientists have sequenced the entire genomes of tumors from 50 breast cancer patients and found more than 1,700 gene mutations, most of which were unique to individual patients. The researchers at Washington University in St. Louis and the Siteman Cancer Center suggest that this variability and uniqueness made it difficult to predict outcomes of the cases.
The team after sequencing the tumor genomes, compared the sequences to the matched DNA of the same patients' healthy cells, which allowed them to find the mutations. They also sequenced the 10 trillion chemical bases of DNA more than 30 times to ensure the data was accurate. All the patients in the study had estrogen-receptor-positive breast cancer, in which cancer cells have receptors that bind to estrogen and help the tumors grow.
Lead investigator Dr. Matthew Ellis, a professor of medicine at Washington University School of Medicine in St. Louis noted that some genetic mutations that are rare in breast cancer are common in other cancers and there may be drugs available to treat them. However, treatment is only possible when the cancer's genetics are known beforehand. The ideal goal is to be able to design treatments by sequencing the tumor genome when a patient's cancer is first diagnosed, Ellis said.
They found a small number of mutated genes that are common to many of the women, including one called PIK3CA and TP53 that other researchers have found play a role in cancer development. Quite a few companies have drugs in development that are designed to target PIK3, which is a signaling pathway that is involved with cancer cell growth. It's estimated that about 40% of women with estrogen-receptor positive breast cancer have a mutation in the PIK3CA gene and about 20% of cases have a mutated TP53 gene. Another mutation was found in a gene called MAP3K1, which controls cell death in about 10% of patients. The mutation allows cells that should die to keep living. Two other genes, ATR and MYST3, were also mutated in about 10% of patients, Ellis said.
However, “to get through this experiment and find only three additional gene mutations at the 10 percent recurrence level was a bit of a shock,” he said. They also found 21 other mutations that appeared at much lower rates in several patients. Even though these mutations were relatively rare, Ellis emphasized the finding's value. “Breast cancer is so common that mutations that recur at a 5 percent frequency level still involve many thousands of women,” he said.
“We get good therapeutic ideas from the genomic information,” he added. “The near term goal is to use information on whole genome sequencing to guide a personalized approach to the patient's treatment.”
The study was presented Saturday (2nd April, 2011) at the American Association for Cancer Research (AACR) annual meeting in Orlando, Fla.
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