The Genome Sequencing Center (GSC) at the School of Medicine has been awarded a $156 million, four-year grant to use the powerful tools of DNA sequencing to unlock the secrets of cancer and other human diseases. The grant is among the largest awarded to the University and one of only three given to U.S. sequencing centers by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health.
The funds also will be used to improve scientists’ understanding of the human genome and to sequence the genomes of non-human primates and microbes.
The three sequencing centers have a proven track record in genome sequencing, which involves spelling out the sequences of letters — A, C, G and T — that make up the genetic codes of all living organisms. The latest funding adds a new dimension to sequencing efforts by focusing on disease genes, particularly those involved in cancer.
“The Human Genome Project gave us the blueprint of the human genome, and now we’re ready to comb that genome to find genetic changes that underlie the development of cancer and sustain its growth,” said Richard K. Wilson, Ph.D., director of the GSC and a leader in the worldwide scientific collaboration that produced the first human genome sequence in 2000. “We strongly believe that a genome-wide understanding of cancer will ultimately lead to the development of new diagnostic tests and more effective treatments.”
The grant underscores the expertise of the center, which has been funded by the NHGRI since 1990 and is a world leader in the innovative high-speed sequencing of genomes, from primitive bacteria to complex humans.
“We are extremely proud to once again play a leading role in genome sequencing, this time with a focus on understanding human health and disease,” Chancellor Mark S. Wrighton said.
“At a time when funding for basic research is declining in real dollars, the grant is a tremendous shot in the arm for Washington University,” said Larry J. Shapiro, M.D., executive vice chancellor of medical affairs and dean of the medical school. “It shows that the National Institutes of Health has tremendous confidence in our Genome Sequencing Center to carry out the next phase of genome sequencing, which is likely to dramatically change the way doctors diagnose and treat disease.”
Genetic errors, or mutations, are known to accumulate in normal cells, ushering in a transformation that can lead to cancer. An estimated 300 genes involved in cancer already are known, and a more in-depth search could identify numerous others that determine, among other things, how aggressive a particular tumor is or which drugs might work best to treat it.
The cancer gene sequencing effort is part of The Cancer Genome Atlas, a joint pilot project of the NHGRI and the National Cancer Institute that will initially focus on identifying small changes, such as duplications or deletions of genetic material, in three types of cancer: ovarian, lung and glioblastoma, an aggressive brain tumor.
The new research involves sequencing a patient’s tumor DNA and comparing it to a normal DNA sample from the same patient to identify changes that may be important to cancer.
“We think that cancer at the level of the genome, while complex, can be characterized,” said Elaine Mardis, Ph.D., co-director of the GSC. “Our funding will be directed at a genome-wide understanding of cancer-specific mutations that, for the first time, will enable us to discover and catalog this information as a first step to finding cancer cures.”
As part of the grant, the center will continue to refine and improve scientists’ understanding of the human genome sequence. WUSTL scientists also will be sequencing the genomes of non-human primates such as the chimpanzee, macaque, orangutan, marmoset and gibbon. Although their genomes closely resemble humans, non-human primates don’t get certain diseases common among humans, such as skin cancer and Alzheimer’s disease, and the researchers hope clues embedded in the genetic sequence will reveal why.
Over the next four years, the centers in the NHGRI program also will mount a major new effort to gather genetic data faster and less expensively than before.
“When we first started genome sequencing in 1990, it took eight years and more than $50 million to produce the sequence of the roundworm C. elegans,” Wilson said. “Next year, we will be testing new technology that would allow us to sequence the C. elegans genome in two or three days at a cost of $5,000. We are continually working to produce sequences faster, better and less expensively.”
The other two sequencing centers funded by the new grant are located at Baylor College of Medicine and the Broad Institute at the Massachusetts Institute of Technology and Harvard University.