Washington University Scientists First to Sequence Genome of Cancer Patient

For the first time, scientists have decoded the complete DNA of a cancer patient and traced her disease - acute myelogenous leukemia - to its genetic roots. A large research team at the Genome Sequencing Center and the Siteman Cancer Center at Washington University School of Medicine in St. Louis sequenced the genome of the patient - a woman in her 50s who ultimately died of her disease - and the genome of her leukemia cells, to identify genetic changes unique to her cancer.

The study is reported in the Nov. 6 issue of the journal Nature.

The pioneering work sets the stage for using a more comprehensive, genome-wide approach to unravel the genetic basis of cancer. "Our work demonstrates the power of sequencing entire genomes to discover novel cancer-related mutations," says senior author Richard K. Wilson, Ph.D., director of Washington University's Genome Sequencing Center. "A genome-wide understanding of cancer, which is now possible with faster, less expensive DNA sequencing technology, is the foundation for developing more effective ways to diagnose and treat cancer."

The researchers discovered just 10 genetic mutations in the patient's tumor DNA that appeared to be relevant to her disease; eight of the mutations were rare and occurred in genes that had never been linked to AML. They also showed that virtually every cell in the tumor sample had nine of the mutations, and that the single genetic alteration that occurred less frequently was likely the last to be acquired. The scientists suspect that all the mutations were important to the patient's cancer.

Like most cancers, AML - a cancer of blood-forming cells in the bone marrow - arises from mutations that accumulate in people's DNA over the course of their lives. However, little is known about the precise nature of those changes and how they disrupt biological pathways to cause the uncontrolled cell growth that is the hallmark of cancer.

Previous efforts to decode individual human genomes have looked at common points of DNA variation that may be relevant for disease risk. What's striking about the new research is that the scientists were able to sift through the 3 billion pairs of chemical bases that make up the human genome to pull out the mutations that contributed to the patient's cancer.

"Until now, no one has sequenced a patient's genome to find all the mutations that are unique to that person's disease," says lead author Timothy Ley, M.D., a hematologist and the Alan A. and Edith L. Wolff Professor of Medicine. "We didn't know what we would find, but we felt that the answers to why this patient had AML had to be embedded in her DNA."

To date, scientists involved in large-scale genetic studies of cancer have not gone so far as to do a full side-by-side comparison of the genomes of normal cells and tumor cells from the same patient. Rather, most earlier studies have involved the sequencing of genes with known or suspected relationships to cancer, a method that likely misses key mutations.