WAYNE FREEDMAN: Hi, I'm Wayne Freedman. Thanks for joining us on this webcast. Lymphoma's like any other disease in that doctors need an accurate diagnosis to give the best and most effective treatment for each patient. So while we spend a lot of time talking about new medications and new treatments, we don't want to overlook diagnostic advances. They are exciting, and they're important, and they didn't get overlooked here in San Francisco when the American Society of Hematology held its annual meeting.
Among the hot topics, something called DNA microarray analysis, which researchers have developed to diagnose large B cell lymphoma. Microarray analysis. That sounds complicated. So what is it? Well, that's why have guests, thank goodness. Here is Dr. Margaret Shipp. She is an associate professor of medicine at the Dana-Farber Cancer Institute at Harvard University. She directs the lymphoma program there. And we have Donna Shu, the president of the Lymphoma Research Foundation of America. Ladies, thank you for joining us.
Doctor, what is a gene chip?
MARGARET SHIPP, MD: A gene chip is a way of being able to understand the message system of a cell. If you think about the way that a cell knows how it should behave, there is basic genetic information encoded in DNA. DNA is then turned into RNA, and RNA is made into protein, and the protein in a cell is actually what makes a cell do -- it's the instructions -- makes a cell do what it should do. What a gene chip allows you to do is to examine those genetic instructions for many of the different genes in the body with a single approach. So the way that this works is that you make from a type of cell that you're interesting in evaluating RNA, and then you have a platform, which is the chip, and that platform has on it representations -- DNA -- for thousands of genes. This is represented in a size that's probably smaller than a quarter. What you can do is you can take the RNA from a tumor cell and overlay it on this chip that has thousands of genes represented, wash it and scan it with a special camera, and get a computer representation of the expression of those thousands of genes just by looking at the information on that chip.
WAYNE FREEDMAN: What do you mean by expression?
MARGARET SHIPP, MD: Expression is an indication of how much of a specific gene product exists in a certain cell, so you get an idea of how active that gene is in a cell. Is it high? Are the levels high? Are the levels low? So you can begin to put together the genetic information by understanding which genes are expressed at high levels, which genes are expressed at low levels, and understand what types of genes are active in different cell types.
WAYNE FREEDMAN: You always get a different road map depending on the tumor?
MARGARET SHIPP, MD: Yes, almost certainly we do.
WAYNE FREEDMAN: So you look at a cell or you look at a plate, and you see the active cells, and then you can determine --
MARGARET SHIPP, MD: Basically what you do is you examine with a single chip the gene expression from all of the different genes that are represented on that chip, so what you can do is get basically a blueprint of the gene activity in a cell by looking at the pattern on the chip. So then what you need to do is you need to compare it to understand how that's similar or different -- different from other tumors, from normals cells, from other types of cancer. So by getting the initial information, and then by comparing that information to similar sorts of information in other tumors and in other normal cells, you can begin to put together stories of how the tumors are different and begin to, from that, understand enough to think about developing treatments that are specifically tailored to the patterns of expression in specific tumor types.
WAYNE FREEDMAN: How many cells are you looking at on one chip?
MARGARET SHIPP, MD: How many specific cells?
WAYNE FREEDMAN: Yeah, how many genes? How many genes are you looking at on one?
MARGARET SHIPP, MD: The technology is improving very rapidly. The type of chips that we have been analyzing have about 7,000 genes on a single chip. There are now chips that include up to almost 20,000 genes on a single chip. The human genetic machinery is thought to probably be included in about 35,000 genes total. We probably only have 35,000 genes total, and so by looking at 7,000 genes you're covering a significant percentage of all of the genetic information, and very soon we'll be able, with a single chip, to evaluate literally the expression of all of the genes that contribute to that information.
WAYNE FREEDMAN: Is it safe to analogize a gene, in this case, as a switch?
MARGARET SHIPP, MD: A gene, I think, would be part of a blueprint, the information that tells you how to function. The information can include switches that should go on, switches that should go off. It's all of the information that a cell needs to operate in the same way that any machine needs certain information in order to be able to operate. It tells a cell to grow. It tells a cell to stop growing. It tells a cell to die, to not die.
WAYNE FREEDMAN: And different types of lymphoma would have a different pattern?
MARGARET SHIPP, MD: Yes. The pattern would be different for two reasons. One would be that the cells that make up the lymphoma are different, and also that there are differences between normal cells and between tumor cells.
WAYNE FREEDMAN: This is still fairly early, right?
MARGARET SHIPP, MD: This is very early. These areearly days.
WAYNE FREEDMAN: Has it affected any treatment yet?
MARGARET SHIPP, MD: It has not affected treatment yet, and I think that we all are hopeful that eventually this sort of information will result in more specific treatments for patients, but it's likely that that process of taking this sort of information and turning it into better, more specific treatments for patients will take several years, but the hope is that we can identify specific characteristics of patients' tumor cells and by understanding those characteristics develop treatment approaches that are designed to affect those processes that have gone wrong in certain types of tumors.
WAYNE FREEDMAN: You're talking about tailor-making treatment?
MARGARET SHIPP, MD: Exactly.
WAYNE FREEDMAN: Specific drugs aimed at specific genes?
MARGARET SHIPP, MD: Exactly.
WAYNE FREEDMAN: Boost them up or take them down?
MARGARET SHIPP, MD: Exactly.
WAYNE FREEDMAN: So it helps you identify lymphomas. And you presented here specifically about lymphomas?
MARGARET SHIPP, MD: About lymphomas, about a specific type of lymphoma. There are many different types of lymphomas, actually -- over 30 different types. But the most common type in adults is a type called diffuse large B cell lymphoma. About a third of all lymphomas in adults are these diffuse large B cell lymphomas, and one of the things that has been most difficult for patients and for doctors who take care of patients is that it's not possible just by making a diagnosis using the techniques that are available now to have accurate information about how well a patient will do with our standard types of treatment. A significant number of patients, actually, can be cured with the types of treatment that we already have available -- about 40% of patients -- but about 60% are not effectively treated and go on to die of their disease. So it would be very important for us to understand what the basis for the differences are between those types of groups, because what we'd like to do is be able to more effectively treat and more specifically treat the tumors from patients that are not effectively treated with our current chemotherapy.
WAYNE FREEDMAN: It tells you which way to go earlier?
MARGARET SHIPP, MD: Correct. Well, it will give us, eventually, information regarding which way to go earlier.
WAYNE FREEDMAN: What's the timeline?
MARGARET SHIPP, MD: The timeline depends on how quickly we can take the information that comes from this type of approach, identify specific ways, specific clues about ways that could be more effective in terms of treating tumors, and then translate that information into treatment strategies. Usually, it's a matter of years to go from an observation about clues, toward clues about better treatments, to actually translating that into better treatments for patients.
WAYNE FREEDMAN: If a person were diagnosed tomorrow, would this affect him at all?
MARGARET SHIPP, MD: Not tomorrow.
WAYNE FREEDMAN: Three years?
MARGARET SHIPP, MD: It's very hard to say. It is a matter of years before this type of technique will affect treatment. It's hard to know whether it's three or five. Some of it's luck. Some of it is the rapid advancement in how we can actually take this information to the clinic. Years.
WAYNE FREEDMAN: It sounds like you've got a tool. I mean, you don't know exactly where you're going to work it yet or how you're going to be able to work it or how far you'll be able to go with it.
MARGARET SHIPP, MD: Well, I think that the value of this sort of approach is that it gives you information about ways to begin to develop more specific treatment approaches, but that process of development is still ahead of us, and that process of development can be shorter or longer, depending on the target that we're trying to hit and the approach that's necessary in terms of actually hitting that target.
WAYNE FREEDMAN: Donna Shu, you're a patient advocate. What do you think?
DONNA SHU: I think the exciting news for the patients here is that at some point in the future physicians will be able to use the technology that Dr. Shipp has been discussing to separate out from this group of diffuse large B cell lymphoma patients those patients who would do well in standard therapy and those patients who would not do well. For those patients who would not do well, investigators will be motivated to search for and identify new targets that they can begin then working on in order to develop new therapies that would be effective and beneficial for this subset of patients that would not do well on standard treatment.
WAYNE FREEDMAN: It sounds like you have a lot of work to do.
MARGARET SHIPP, MD: We do.
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