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Our News - In Their Own Words - Staudt Interview

Genomic Profiling

NOTE: This interview is an excerpt from NIH Radio Podcast, Episode 25

Bill Schmalfeldt:
It took me a while to get here: every time I come to the Clinical Center here at the Campus of the National Institutes of Health, I find myself lost in the wandering, labyrinth-type hallways. And after the third set of directions, I finally found my way to the office of Doctor Louis M. Staudt. He’s the Chief of the Lymphoid Malignancy Section of the Metabolism Branch at the Center for Cancer Research of the National Cancer Institute. And the reason we’re sitting down today is to discuss the concept and the applications of genomic profiling. Now if you’re listening to the Podcast, obviously you’re interested in science on a layman’s level or even as a professional. But for a layman such as myself, as soon as I hear the words, “genomic profiling,” my eyes glaze over a little bit and it feels to me like somebody’s going to be talking about something and I have no idea what they’re talking about. Could you give us a quick layman one-on-one discussion on what we mean by genomic profiling?

Dr. Louis Staudt:
Sure. Well, as a consequence of the completion of the human genome project, we’ve been blessed with the knowledge of 20 to 30,000 genes encoded in our DNA. And the basic idea is that every cell in our body has that same DNA, those same 20 to 30,000 genes. And they’re instructions for how a cell works, but why is it then, that a brain cell is different from a white blood cell? It’s quite simply that the brain cell chooses a different subset of the 20,000 genes to create its unique properties to be able to signal and make memories and the like. Whereas the white blood cells chooses a different set of those genes and they’re, including genes and coding, antibodies that are used to fight off infections. So because we have such a diversity of cells in the body, we use, we make subsets of the genes active. And gene expression profiling is a technology that allows us to determine which subset of the genome is active in a given cell type at a given time.

Bill Schmalfeldt:
Well, in the treatment of diseases, how can genomic profiling be turned into a very important tool?

Dr. Louis Staudt:
We were struck by the fact that cancer was a very heterogeneous disease and that although we are able to cure some individuals with cancer, others unfortunately succumb to the disease. And so, an early idea that we had was whether the -- by profiling the activity of genes in cancer biopsy samples from individual patients, could we discover why it was that one cancer is curable and the other not. And that turns out to be case.

So in our particular work, we’ve looked at lymphomas, cancers of the B-lymphocyte. In particular, the most common type of B-cell lymphoma is called diffuse large B-cell lymphoma. It’s a very aggressive disease, but fortunately can be cured with combination chemotherapy these days. But approximately 50 percent of individuals with this disease are cured and the other 50 percent, not. So by collecting biopsy samples from hundreds of patients with diffuse large B-cell lymphoma, we then looked at the activity of genes in those samples by gene expression profiling. And were easily able to discern two major subgroups within the diffuse large B-cell lymphomas. And then when we looked at the clinical response of those patients to chemotherapy, we found one subgroup had a much more favorable response to chemotherapy and the other subgroup had a cancer that was much more difficult to cure.

Bill Schmalfeldt:
So if I’m understanding this then, by looking at the blueprint of the gene, you’re better able to answer some of the questions as to why a cell acts in a certain way, and that helps in the treatment of such a disease as lymphoma.

Dr. Louis Staudt:
That’s right. In essence, the wiring diagrams inside the cancer cells of one patient will be different than the cancer cells in another patient. And the gene expression patterns that we see are sort of the outcome of that different wiring and also create the different wiring within the cancer cell. So it is in fact, as you put it, a blueprint for differences in the wiring diagrams of cancer cells.

Bill Schmalfeldt:
Now, do you envision a day, as this science progresses, that a person will go in to -- for a regular visit, to a doctor, and have his blood drawn, give a urine sample, and maybe submit some tissue for genomic profiling?

Louis Staudt:
So we’re working to that end very vigorously. So my view is that, within five years, most cancer types will be diagnosed with this so-called molecular diagnosis. So currently cancer is diagnosed by the appearance the tumor, by the appearance of the cells within the tumor under the microscope. But this is not a quantitative method and in many cases, may lend itself to incorrect diagnoses, whereas the gene expression profiling being quantitative, being highly reproducible, has the potential to transform the diagnosis of cancer. So we and other groups are working to make designer DNA microarrays that could be used for the diagnosis of cancer. And so the sample of tissue taken from the cancer would be plopped onto, in a test tube and frozen on dry ice and sent off to a reference laboratory, which would perform the gene expression profiling on this designer microarray. And the diagnosis, calculated mathematically, in fact, would be delivered back to the physician, who would then relay that to the patient and determine the course of treatment.

Bill Schmalfeldt:
Maybe I’m talking science fiction here, somewhere down the road, but is there a day in the future, foreseeable, where a person can undergo genomic profiling and be identified as having a particular risk for a certain kind of cancer?

Louis Staudt:
So that’s a definite possibility, certain genes predisposed to certain types of cancer. And in fact, we do that on a gene-by-gene basis now in certain cancer families, or patients with families that are at risk for, let’s say, colon cancer or breast cancer. More broadly though, we’re now able to look at variation in genes across the genome. This is a little different than I was talking to you about before, though. This is not necessarily the expression of the genes, but also their function. And in the human population, they’re very many different forms, if you will, of the same genes, slight variants. And these are caused by single changes in the DNA sequence in the same gene in different individuals. And that indeed could be used in the future to assess one’s risk for not just cancer, but many different types of disease.

Bill Schmalfeldt:
What are some of the big, unanswered questions at this point?

Louis Staudt:
The unanswered questions are how we can go towards finding better cures, based on this knowledge. They’re not completely unanswered, because we have -- we’re approaching that question so we use other aspects of the human genome to find out which are the critical pathways that a cancer cell depends on for its overabundant proliferation and its inappropriate survival as a cell. And we have methods by which we can inactivate single genes within the cancer cell and ask what happens. So we can find which genes are so critical for the survival of cancer that they could be called the Achilles heel of the cancer cell. And of course, if one could attack the protein products of those genes with a drug, then that might be a successful new way to cure the cancer.

Bill Schmalfeldt:
And the voyage of discovery goes on here at the National Institutes of Health. Doctor Louis M. Staudt, Chief of the Lymphoid Malignancy Section, Metabolism Branch, Center for Cancer Research here at the National Cancer Institute. Thanks for spending some time with us today on NIH Research Radio.

Dr. Louis Staudt:
It’s been a pleasure.

[end of transcript]

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