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Home > ARRA Stories > Dr. William Hahn: Scanning Cancer Genomes for Disease Genes and Drug Targets
Dr. William Hahn: Scanning Cancer Genomes for Disease Genes and Drug Targets

By Alison Davis

April 30, 2010

Photo of Dr. William Hahn

Dr. William Hahn

William C. Hahn, M.D., Ph.D., Associate Professor, Medicine, Harvard Medical School and Dana-Farber Cancer Institute, Boston, Massachusetts.

Because cancer is basically a disease of DNA, differences in genes between tumors can serve as identification for different types of tumors. The Cancer Genome Atlas, or TCGA, is a new project that aims to fingerprint different types of cancers. Oncologist Dr. William C. Hahn is hard at work developing powerful tools to turn this information into a new generation of cancer therapies, diagnostics, and preventive strategies.

The Problem: Comprehensive efforts to determine the DNA, or genomic, sequences of tumors taken from people with various forms of cancer are under way as part of TCGA. This project and others like it are important in that they provide researchers with an ordered sequence of DNA letters for specific types of cancers.

But the gene readouts are less like instruction manuals than they are like Scrabble tiles that need to be assembled to make sense. What's more, even though scientists know that the DNA in tumor cells contains thousands of individual changes, or mutations, how do you know which ones are important and which ones are false leads? Imagine a hallway with many doors but only one that opens to let you out.

Finding a Solution: Dr. William C. Hahn is looking for the cancer genes that matter — the ones, for example, that drive a cell to divide out of control, cause the cancer to spread to other tissues, or attract nourishment from blood vessels, prompting further growth. Dr. Hahn, who is both a physician and a scientist, sees his two hats as synergistic for making progress in his research.

"I regularly see individual cancer patients in the clinic," Dr. Hahn says, "but by doing genome-scale experiments, I see the opportunity to help patients with all types of cancer."

Knowing the sequences of the genes is an essential first step, but the hard part is figuring out what they do. Dr. Hahn's method is comprehensive, yet efficient. To make the two-year project doable, he has focused his efforts on two cancer types: ovarian cancer and glioblastoma, the latter one of the deadliest forms of brain cancer.

He uses lab-grown cells that genetically match each tumor type, and then he uses molecular tricks to turn individual genes on or off while he measures the effects — all at once. In this way, Dr. Hahn can get a handle on the function of individual genes.

His approach is different from most others, Dr. Hahn explains, because many projects to date have been able to look at only one gene or just a few genes at a time. He's looking for the genes that cause a cell to die (potential drug targets) and the ones that cause a cell to grow out of control (the disease genes). The project is massive, because Dr. Hahn is investigating 30 cell lines for ovarian cancer and another 30 cell lines for glioblastoma.

"Ultimately, we need to be able to subtype tumors in order to know how to treat them," Dr. Hahn explains. "Classification by molecule or gene will probably be more important than classification by organ, such as brain, cancer, or ovary."

How This Funding Helps: Dr. Hahn says that although he has wanted to do this project for some time, Recovery Act funding made it possible. Part of the reason is that it's a project that involves a coordinated, large-scale effort and a lot of people working toward a specific goal, not just people focused on advancing their own individual projects.

"This was a perfect vehicle for putting people to work on a project they were really interested in," Dr. Hahn says

He adds that his approach and the results will likely serve future needs by helping to create a market for people who have developed the skill set for performing large-scale studies, and by training people in this type of work.

After Two Years … All of the data collected will be publicly available so that scientists everywhere can continue research on the causes of glioblastoma and ovarian cancer and also look for customized treatments that target mutated genes or sets of genes that Dr. Hahn's scanning method has identified.

Recovery Act Investment: "Functional Annotation of Cancer Genomes: TCGA, Glioblastoma, and Ovarian Cancer," $2,998,132 for FY 2009. Funded by the National Cancer Institute.

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