In a second case, Wilson and collaborators at Washington University sequenced the cancer genome of a 39-year-old woman with an unusual case of acute myeloid leukemia (AML), a disease that originates in bone marrow and grows from blood-forming stem cells. Wilson’s team has sequenced about 50 AML cancers, most purely for research; this was the first instance of trying to use the findings to aid a patient.
Physicians currently try to predict the prognosis for patients with different subtypes of AML by looking for certain abnormalities in their chromosomes. One common abnormality–a fusion of two different proteins–means that the patient is likely to respond to a drug called all-trans-retinoic acid (ATRA), which replaces the role of one of the proteins mutated in the fusion. “ATRA is basically a cure for people with this fusion,” says Elaine Mardis, another senior scientist on the study.
Standard testing showed the patient did not have the typical fusion, but genome analysis revealed that she had a never-before-seen version of it not detectable with the other test. She was given the drug and has been in remission for several months. “I’m not trying to hype it at all, but the treatment saved the patient’s life,” says Wilson. Adds Mardis, “This might be the watershed event that makes cancer patients begin to ask for this.”
The researchers are now looking at other patients with unusual cases of leukemia and are working on a simple test to detect this more unusual form of the fusion, without whole genome sequencing. “If they have truly found a new marker, that is something that could be tested in the clinic immediately,” says Jones. “This is an example of an incredible stride forward for the field.”
The opportunity to use whole genome sequencing to help cancer patients is still extremely rare. It’s limited to medical centers with large sequencing facilities, the funding to undertake such a project, and ethical review procedures in place to assess and approve this type of experimental approach. But the cost of sequencing itself–about $10,000 to $20,000 for a human genome–is quickly becoming less of a roadblock. It’s now on par with other medical tests and treatments for cancer; an MRI scan costs about $6,000, and cancer patients typically have several. But both Jones and Wilson point out that the process of interpreting the genome and using it to make decisions is still very labor-intensive, requiring a large team with diverse expertise in medicine, oncology, genomics, and information technology.
Some scientists are concerned that the research is too preliminary to be applied to patients, and that its success will be difficult to evaluate. Commenting broadly on the concept of using whole genome data to guide treatment decisions, David Altshuler, a geneticist at the Broad Institute, in Cambridge, Massachusetts, points out that it’s impossible to conclude from individual cases whether a particular treatment worked because of a mutation identified in the genetic analysis. It might have worked for some other reason. The scientists carrying out the research say that these patients have no other options, and that the genetic information is just one piece of data that might help doctors chart the best course.