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‘Armamentarium’ for personalized medicine
September 2013
by Amy Swinderman  |  Email the author


Despite widespread fear over the impact that the government sequester is having on already stretched-thin funding for U.S. biomedical research, the world of genomic sequencing got a boost last month when the U.S. National Institutes of Health (NIH) awarded four grants to multidisciplinary research teams to explore how genome sequencing can be used to advance medical care.  
The new grants, funded as part of the National Human Genome Research Institute's (NHGRI) Clinical Sequencing Exploratory Research (CSER) program, total approximately $6.7 million in the first year, and if funding remains available—and that could be a big "if" should the sequester continue to plunder federal research grants—could total approximately $27 million over four years.  
The new grants expand on the initial CSER program awards given to six research teams in December 2011, including approximately $5 million from the National Cancer Institute. Since that time, the use of clinical genome sequencing has seen tremendous growth, says Dr. Bradley Ozenberger, CSER program director and deputy director of the Division of Genomic Medicine at NHGRI.  
"The cost of genome sequencing has dropped so precipitously in recent years that there is an explosion of genomic medicine—or precision medicine—to bring the option of applying this knowledge to the care of individual patients," Ozenberger says.  
The areas of research being pursued by these new projects include using genome sequencing to inform couples about reproductive risks, determining the genetic causes of childhood developmental delays and communicating findings to parents and detecting genomic alterations that can lead to cancer. But the focus of these projects will not be on developing technologies, Ozenberger notes.  
"It's not so much that we need an effort like this to develop technologies," he says. "We do still need to develop ways to put genomic information into a patient's medical record, but the exploratory need is that the psychosocial and ethical components of this. Technology is outpacing that. We can sequence a person's entire genome, but more importantly, their exome. There are all kinds of unintended or unanticipated results that come out of that. How do clinical labs communicate to physicians, how do physicians communicate with patients, what do patients want to hear?"  
In the first project, which has been awarded $8.1 million, the Kaiser Foundation Research Institute in Portland, Ore., will examine the use of whole-genome sequencing in informing couples, before they conceive a child, about their potential carrier status for genetic disease. They will compare women and their partners who receive preconception genetic testing to those who receive whole-genome sequencing in addition to the testing.  Scientists will look for genetic mutations for about 100 rare conditions and expect to enroll 380 people in the trial. Couples with mutations that put children at risk for a condition will work with a genetic counselor and complete surveys to help researchers develop useful approaches to presenting information to patients.  
In the second project, which will receive $7.66 million, the Hudson-Alpha Institute for Biotechnology in Huntsville, Ala., will sequence the genomes of nearly 500 children with developmental delays and other disabilities, along with their parents, in the hopes of discovering genomic alterations behind such disorders. The researchers hope to uncover gene alterations that are common to more than one condition and gain insights to whether certain mutations cause milder or more severe cases of some conditions.  
In the third project, awarded $7.97 million, principal investigator Arul Chinnaiyan and his team will sequence the genomes of tumors from 500 patients with advanced sarcoma or other rare cancers to discover new information about genomic alterations, with the goal of eventually customizing therapies. Few clinical trials have been conducted in most rare cancers, and scientists would like to know more about the genetic underpinnings of these diseases. Investigators also plan to evaluate the patient consent process, and the delivery and use of genome sequencing results.  
Finally, in the fourth project, the recipient of $3 million, researchers at the University of Washington will lead the coordinating center responsible for pulling together all of the scientific teams, helping to organize studies, interpreting study results and helping groups focus on common goals. The coordinating center team members bring their own expertise in clinical genetics, genome sequencing, bioinformatics and ethics.  
"These projects were planned out prior to the sequestration," Ozenberger points out. "These are four-year awards, so the program will wind down in three to four years­—but the work will not be done, certainly not in such a complex field where we are striving for a societal impact on clinical care."   Ozenberger, who was an investigator for both the Cancer Genome Atlas Project and at Wyeth Pharmaceuticals, says he expects these efforts to have an eventual impact on drug discovery and the advent of personalized medicine.  
"There is a bit of a lag as pharma companies use data and develop therapeutics, but soon, drug discovery and technology will merge so we have an armamentarium," he says. "When you think of projects like the Cancer Genome Atlas, there is so much discovery that has been empowered by that data. Now, the big challenge is that if we sequence your breast cancer tumor and discover 120 mutations there, we can probably sort through the four that are really important to the progression of that cancer, but now we need the drugs. We don't always have drugs specific to that aberration."  
The major impact that genome sequencing is expected to have on drug discovery or personalized medicine is in cancer, according to Ozenberger.  
"Cancer is a disease of the genome," he says. "We need to understand that we need to consider each individual person's individual tumor as a separate thing. That is where genome sequencing for patient care is being applied most broadly and quickly. We envision a time where we can use our genomic data for care throughout life. There will come a time when each person has a genome sequence as part of his or her medical record. This will allow us to customize medications for them, and even adjust their lifestyle.
"We're really at the dawn of this new age of both genetic discovery as well as genomic medicine. Obviously, this is very exciting, but what will be most exciting is the ultimate benefit to public health," he concludes.  
Code: E091321



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