In the fall of 2006, a new machine arrived at what’s now known as the Genome Institute at Washington University in St. Louis. It was capable of reading DNA a thousand times as quickly as the facility’s earlier machines, and at far less cost. Elaine Mardis, the center’s codirector, immediately began using it to sequence cancer tissues, scouring their DNA for mutations. Just five years later, Mardis and her collaborators have sequenced both cancerous and healthy tissue from several hundred patients and identified tens of thousands of mutations. Some of the findings have led to new approaches to treating cancer, while others have opened new avenues of research.

Cancer develops when cells accumulate genetic mistakes that allow them to grow and divide faster than healthy cells. Identifying the mutations that underlie this transformation can help predict a patient’s prognosis and identify which drugs are most likely to work for that patient. The information could also identify new targets for cancer drugs. “In a single patient, you have both the tumor genome and the normal genome,” Mardis says. “And you can get at answers much more quickly by comparing the two.”

In 2008, Mardis and her team became the first to publish the sequence of a cancer genome, derived by comparing the DNA of healthy and cancerous cells in a patient with a bone marrow cancer called AML. Further studies have suggested that patients with mutations in a particular gene may fare better with bone marrow transplants than with traditional chemotherapy, a less risky treatment that physicians usually try first. Mardis predicts that soon all AML patients will be genetically tested, allowing their physicians to make more informed decisions about treatment.

As the cost and speed of DNA sequencing have dropped—Mardis estimates that sequencing genomes from a patient’s cancerous and healthy tissue today costs about $30,000, compared with $1.6 million for the first AML genome—the technology is being applied to oncology more broadly. Research groups have now sequenced the genomes of multiple cancers, and in a handful of cases, they have used the results to guide treatment decisions for a patient (see “Cancer’s Genome,” January/February 2011). A few companies are now offering cancer genome analysis to researchers, and at least one is planning to offer the service to physicians and patients.

The decreasing cost of sequencing also means that Mardis can use the technology in drug development and testing. Her latest project is part of a clinical trial assessing hormone therapy for breast cancer. She has developed a preliminary genetic profile of cancers most likely to respond to a popular set of drugs called aromatase inhibitors, which are given to most breast cancer patients whose tumor cells have estrogen receptors on the surface. The goal is to identify the patients who will benefit from the drugs and those who won’t. (Preliminary evidence suggests that only about half the patients in the trial respond to the drugs.)

Understanding cancer genomes isn’t easy. Mardis’s team had to invent techniques to distinguish the rare cancer mutations from the mistakes that routinely occur when sequencing DNA. And scientists must figure out which mutations are actually driving the growth of the tumors and which are harmless. Then comes what might be the most challenging part: determining how the mutations trigger cancer. Mardis says she is leaving that challenge to the scientists around the world who are working to understand the mutations that she and others have identified. “It’s really gratifying to see others pick that up,” she says.