One of the prime reasons for justifying the massive international effort to determine the complete DNA sequence of a human being was the hope that knowledge of a person’s individual genetic composition would lead to a more individualized and effective approach to medicine. In the 10 years since the first complete human genomic DNA sequence was published, what progress has been made toward this goal of a personalized medicine based on a person’s genotype or genetic makeup?

An opportunity to assess this progress was provided by the recent “Future of Genomic Medicine IV” meeting in La Jolla, California, organized by the Scripps Translational Science Institute. To illustrate how the practice of medicine is or will be impacted by the application of genomic information, here are some highlights of the data that were presented at this year’s meeting.

In a previous blog, we discussed genetic variants in the CYP2C19 gene which affect the individual’s ability to metabolize the anti-platelet drug called clopidogrel (Plavix) to its active form. At the meeting, Dr. Matthew Price of Scripps Translational Science Institute and Scripps Clinic suggested the need for setting up a rapid point-of-care genotyping system for clopidogrel response testing for patients who have acute coronary disease that may require surgical intervention. He argued that there is a need for infrastructure and technology for bedside genotyping within hours of the cardiac event.

While such rapid point-of-care genotyping machines are still being developed, the technology is currently available for proactive genotyping of patients before they enter the emergency room; this approach gives doctors the results they need when they need it most.

Of particular interest is an approach described below by Dr. Valantine and by Dr. Shak which synthesizes or integrates information from the expression pattern of multiple genes. This is a step away from the traditional testing of single genes and toward a true “genomic” (multigenic) test.

The main risk for heart transplant recipients is rejection of the transplanted heart by the patient’s immune system. Dr. Hannah Valantine of the Stanford University Medical School described a new technique for ascertaining the rejection status of a transplant by examining the pattern of gene expression of immune response genes. This noninvasive gene expression profiling technique using a sample of the patient’s blood is much easier to tolerate than the previous standard method of using a catheter to take a direct biopsy of the heart muscle.

Although only 4% of breast cancers respond to chemotherapy, doctors used to feel obligated to initiate chemotherapy on the small chance that the treatment would work. Dr. Steve Shak described a test (OncotypeDX) that identifies breast cancer patients who will respond to chemotherapy based on the expression pattern of 21 specific genes in tumor biopsy samples. This commercial test, which has been administered more than 125,000 times since 2004, also estimates likelihood of breast cancer recurrence.

In another presentation at the meeting, Dr. Howard Jacob of the Medical College of Wisconsin described the case of Nicholas Volker, a young boy who had endured 100 surgeries in six months in a fruitless attempt to treat a mysterious intestinal disease that baffled his doctors. As a last resort, his doctors came to Dr. Jacob for help in determining if there was a genetic basis for his condition. Because the technology was available, they determined the complete DNA sequence of every protein coding segment in the boy’s genome and found a potential disease-causing mutation in the XIAP gene. Based on knowledge of the XIAP gene, they decided to try a bone marrow transplant. Against all odds, the bone marrow transplant worked and Nicholas Volker made medical history as the first patient to be diagnosed and cured as a result of whole exome sequencing.

As you can see from these examples, genomic information is already being used to improve the practice of medicine. Pathway Genomics is constantly surveying the scientific literature to incorporate the latest research findings into our genetic tests to give you and your physician actionable information that you can use to improve your lifestyle and to make better health decisions.