Study examines link between genetics and cancer

| News Editor

Washington University has undertaken an unprecedented study of cancer tumors with the help of St. Jude’s Children’s Hospital in an effort to pinpoint genetic mutations that play a role in causing cancer.

Richard Wilson and the Genomics Sequencing Center at the University are handling the sequencing of all 600 tumor samples that will be studied during the three-year project. The first few tumors are already being analyzed. The first 50 tumors will be sequenced and analyzed within the first year of the study.

“There have been all kinds of studies that call themselves cancer genomics studies,” Wilson said. “Most of them have looked at small numbers of genes that are genes we know are involved in various types of cancer, and the idea is simply to look at those cancer patients and see if you can find mutations and say you know what caused this person’s cancer.”

What sets the study apart from previous projects is its scale. Samples from 600 patients will have their entire genomes sequenced in three years.

“To actually look at whole genomes for 600 patients is really unprecedented,” Wilson said. “You can look at a few genes in a lot of patients, or you can look at a lot of genes in a smaller number of patients. Those two extremes have been what’s been done so far.”

Wilson said that the study is taking a broad look at the genome without preconceived ideas about what genes might be more likely to play a role.

“Every type of cancer is different,” he said. “If you know of some genes that are mutated in lung cancer and then you go study breast cancer and you only look at those genes, you probably won’t find much. There may be some overlap, but for the most part, different cancers are caused by different gene mutations. We learned that we really needed to look at all genes, so this is really a science that’s been pioneered here at Washington University. Throw a rope around the entire genome and determine what mutations may have occurred.”

Since the study is so over-arching, there are unique challenges that Wilson said the team is prepared for.

“It’s like taking two haystacks and trying to find the bits of hay that are different in the second one,” Wilson said. “It’s an enormous computational problem. The human genome is 3 billion bits of information. Most of the software we utilize for the analysis is stuff we’ve developed over the last few years.”

Wilson said that while the University will analyze the tumors, St. Jude’s plays several critical roles.

“It sounds like it’s straightforward, but it’s not so simple,” he said. “There are a lot of careful methods you have to utilize to preserve the tumor sample. There’s an amazing amount of clinical information. We’ll work together on some downstream experiments. It’s going to be a really nice collaboration.”

The project’s goal is to try to identify genes that play a role in cancer so they can be a target for future treatment. Wilson mentioned that there have already been gene mutations that affect responses to certain drugs.

“In the long term it helps you better understand the disease so you can think about new drugs that might be even more effective or even better, are targeted to the patient’s exact mutation, and you’ll be able to dial in exact treatments,” he said. “What we learn in the short term is how to better utilize the drugs we already have.”

The study divides the tumors into three broad areas: leukemia, brain tumors and solid tumors, in other places, known as sarcomas.

Wilson added that holding the study in St. Louis has been advantageous.

“St. Louis is really one of the only places where this could happen,” Wilson said. “We’ve pioneered these methods. People at Wash. U. should be proud that we’re leaders in this field.”