FT. LAUDERDALE, Fla. _ Prostate cancer is the paradigmmolecular geneticist Leroy Hood has chosen to deploy the three mostbasic genomic tools for stratifying disease.
In a talk on "Genomic approaches to diagnostics and therapeutics,"Wednesday at the 1996 Miami Bio/Technology Winter Symposium,he said, "These are large-scale DNA sequencing, genome-widegenetic mapping, and very large DNA arrays, for interrogatingcomplex systems and networks." He made the point that "All theseare techniques that have come right out of the Human GenomeProject."
Hood, who chairs the molecular biotechnology department at theUniversity of Washington School of Medicine, in Seattle, emphasizedthat "this approach is independent from dealing with the classicalcancer triad of oncogenes, tumor suppressors and DNA repair," butadded, "That doesn't mean to say they don't have very importantthings to add." He said that "with the triple approach we've definedhere, we are pointing much more toward things that are going to beclinically relevant in the future.
"The days when you could study one gene and one protein, and hopeto understand biological and medical things, are I think starting tofade now. Not that it isn't important to do that, but you aren't goingto understand prostate cancer, by studying any one single gene," hesaid.
Hood has organized a consortium of academic scientists across theU.S., including specialists in genetic mapping, expression mapping,molecular biology, urology, prostate tumor banking andepidemiology.
Coast-To-Coast Prostate Task Force On Station
"We're taking the three approaches to the prostate cancerstratification program," Hood told his audience: "One, incollaboration with Janice Stanford at the Fred Hutchinson CancerResearch Center, in Seattle, is to use epidemiological techniques tolook at 2,000 consecutive prostate tumors, and ask: How do theydiffer from one another, either in their history or their progression?"
His second approach, with members of the nationwide consortium,"is that we're going to be assembling, in time, a thousand familiesthat have three or more affected members with prostate cancer. Then,using these genome-wide techniques, we'll divide prostate tumorsinto discrete groups, which will be the same as the third approach,using these large-scale DNA arrays to interrogate the messenger-RNA information that's present in the 600 different tumors."
As things now stand, Hood said, "we have about 350 families, andwe're just beginning to prepare the DNAs, to do the genetic analyseson. The prostate cancer consortium we've set up has two majorcenters, the University of Washington, in Seattle, and WashingtonUniversity, in St. Louis. We've charged them with beginning tocollect these 600 or more pure tumors on which to do the analyses."
Enlisting The Media For Families, Funding
Hood appeared on CNN last November, together with retired generalNorman Schwartzkopf and financier Michael Milliken. Theypromoted the prostate program, and invited prostate families to comeforward.
"I had met Michael Milliken back in `86 or `87," Hood toldBioWorld Today. "I realized he was very interested in supportingprostate cancer, and a collaboration with him represented anattractive possibility for creating the resources." Milliken'sfoundation, CapCure, is dedicated to finding research money forprostate cancer. "This year," Hood said, "our consortium is going toget somewhere around 2.5 million dollars from it."
He also said that a national news weekly is planning to showcase theprostate project in a cover story next month.
"Prostate cancer is an interesting tumor," Hood observed. "It's notthe leading killer, but it is the commonest cancer among Americanstoday. Breast cancer is second."
Stratification Strategy Spelled Out
Elaborating on his idea of disease stratification, he predicted that"prostate cancer is going to be three or four or five different diseases,and that the very powerful tools that have emerged from genomicsare the means by which we can, first of all, carry out the stratification,create diagnostic markers, so we can say: `This is a very malignantform of prostate cancer, and this is a very benign form, we shouldtreat and not treat respectively.'"
Hood explained that "in prostate cancer it's really critical to be ableto distinguish the benign tumors from the really malignant ones.Because if you undergo a radical prostectomy, there's a reasonableprobability you'll have complications _ impotence, incontinence,things like that. So we'd like a simple diagnostic that can say: "Don'ttouch this one," or, "Do something immediately."
In his talk, Hood alluded to the futurist concept of a diagnostic chip."These were pioneered by Affymetrix Inc. [of Santa Clara, Calif.],"he said. "You can synthesize oligonucleotides on small, one-centimeter chips of glass or silicon. For example, they couldrepresent unique portions of oncogenes, or diagnostic markers. Youcould create a chip that had all of the diagnostic markers for the 20most common kinds of cancer."
He continued: "The point is, you could for one thing do simple bloodtests, PCR analyses to interrogate normal patients to see if in factsequences were showing up in their blood that didn't belong there,that were pathognomonic to tumors. And the assay is molecularhybridization, complementarity of DNA."
A question from the floor asked Hood to assess the role ofenvironmental carcinogens, such as radiation or chemicals.
He replied that, "the environment plays a really important role incancer," but added, "A lot of disease can be manipulated byunderstanding its molecular basis, just circumventing thesusceptibility our genes provided for certain environmentalcarcinogens."
On the environmental issue, Hood also agreed that "we shouldn'tgive up educating people to give up smoking," but concluded: "I'mskeptical that we can induce the population to resist temptations, so itwould be nice to have little pills that can deal with deficiencies ourgene predispositions provide us with." n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.