From human genome to cancer genome
Dr. John McPherson (centre) with research technicians Dr. Philip Zuzarte and Ada Wong at work in the OICR cancer genomics laboratory.
(CPimages/D. Oliver)
The era of truly personalized cancer-fighting tools may not be here yet, but Dr. John McPherson, Director of the Ontario Institute for Cancer Research’s (OICR) Cancer Genomics Program, says patients will start to see major benefits from genomic research well within a decade.
In collaboration with the Informatics and Biocomputing Platform, McPherson’s lab will make OICR’s contribution to the International Cancer Genome Consortium (ICGC), announced in April. His team will focus on pancreatic cancer, one of the 50 most common types of cancer that will be studied in the major international research initiative. McPherson hopes to identify variations in the genetic code that may cause pancreatic cancer or increase individuals’ risk of developing the disease.
McPherson, a Canadian who returned to Ontario last year after spending 20 years in the United States, has worked on some of the most significant scientific projects in recent history, including the Human Genome Project. Combined with the International HapMap Project, these research efforts have aimed to create a map of all the common variations in the human genetic code – of which there are millions.
One of the greatest challenges for McPherson and other colleagues who want to apply the knowledge gained in the Human Genome and HapMap projects is that many variations occur naturally among healthy individuals. This makes it harder to identify and isolate the genes that are associated with diseases like cancer.
“The Human Genome Project was a great advance, but it didn’t take us as far as we would have liked. We now know that the ‘normal’ genome is actually something that varies quite a bit, so personalized medicine could never be as simple as comparing your own genome to what’s normal and immediately understanding what diseases and risks of developing disease you have,” explains McPherson.
The purpose of the ICGC is to understand which genetic variations matter. Researchers will do this by sequencing 500 samples of the 50 most common types of cancer. They will then compare genetic data from these samples to genetic data from healthy tissue in order to find which genes are most commonly associated with cancer.
“The ICGC’s approach acknowledges that we need to do a lot more sequencing than we initially imagined if we want to understand the genetics of common cancers. The first genomic cancer studies involved comparisons of small numbers of samples – 10 healthy and 10 diseased, for example. We now know we need to do hundreds of sequences to isolate the genetic sequences that are strongly associated with cancer and distringuish them from all of the random genetic variations that occur naturally from sample to sample” says McPherson.
Genomic sequencing technology is keeping pace with these developments, making it possible to conduct ever-larger studies. Dr. McPherson’s team is currently testing a new generation of genomic sequencers; these machines reduce the amount of time it takes to sequence an entire genome from months to a day and a half. When fully operational, OICR’s next-generation sequencing platform will give it one of the highest capacities of any genomics laboratory in the world.
With technology moving at this pace, McPherson says there is every reason to believe that the information we need to develop a new generation of cancer fighting treatments is within our grasp. But he cautions that no matter how revolutionary genomic sequencing may be, applying it to the clinic requires an enormous amount of basic scientific knowledge, technological innovation and clinical research – which cannot be developed overnight.
“One of the most high-profile concepts in science right now is the ‘thousand dollar genome,’ the idea that if we can lower the cost of sequencing the genome to $1000, we could sequence the genome of every individual. But even if we got to that point tomorrow, there’s very little that a doctor can do with that information because we still have so much to learn about how our genes function and interact,” he says.
“Some clinical applications have already been developed from the knowledge that we do have of the genome and many more are on the horizon, but we are still very much in the early stages. There is a lot of work to do before we get to the point where we can sequence someone’s genome and know their risk for a whole range of diseases and know what treatments they’ll respond to if they get those diseases,” he says.
Yet only five years ago, studies like the ICGC would have been impossible. At this pace, it’s easy to understand why McPherson is confident he and his colleagues will be able to undertake the great amount of work that will eventually lead to personalized treatments for cancer. With his extensive experience in genomics research and a new state-of-the-art laboratory, Dr. John McPherson is well equipped to make important new contributions to our understanding of the genetic basis of cancer.
In profile
Dr. John McPherson
| 2003 - 2007 | Associate Professor: Baylor College of Medicine. Primary appointment: Department of Molecular and Human Genetics. Joint appointment: Human Genome Sequencing Center |
| 2000 - 2003 | Associate Professor: Washington University School of Medicine. Primary appointment: Division of Biology and Biomedical Sciences, Department of Genetics. Joint appointment: Genome Sequencing Center |
| 1999 - 2003 | Co-Director, Genome Sequencing Center: Washington University School of Medicine |
| 1993 - 1996 | Co-Director, National Human Genome Research Center at UCI: University of California at Irvine |
| 1988 - 1990 | Postdoctoral Fellow, University of California at Irvine, Department of Pediatrics |
| 1990 - 1992 | Postdoctoral Fellow, University of California at Irvine, Department of Biological Chemistry |
| 1989 | PhD, Biochemistry, Queen’s University |
Click here to view Dr. McPherson's page on the OICR website
