| | | |
|
|
|
|
|
|
THE FINDING, released Monday, marks the culmination of five years of study by a team at Long Island's Cold Spring Harbor Laboratories led by Michael Wigler.
While it will likely take even more years before the discovery turns into a new therapy if it gets there at all researchers say they believe the techniques they are using that helped them find this gene will eventually produce a map of all the chemical events underlying cancers. That information is crucial to designing new ways to diagnose and treat, and maybe even prevent the deadly diseases. |
|
|
|
Advertisement
|
|
The Cold Spring Harbor team believes the gene identified in this latest
discovery, primarily the work of Dr. Masaaki Hamaguchi, is one of a host
of genes in breast cancer that, when damaged, allow a normal cell to multiply
out of control and over time become life threatening.
Drs. Wigler and Hamaguchi have dubbed the new gene DBC2, an abbreviation of "deleted in breast cancer." They include the number 2 because it is the second of such deleted, or missing, genes in breast cancer cells to be found in their labs. DBC1, the researchers say, has not yet been linked to breast cancer.
DBC2 is being added to a small but growing list of other breast cancer genes found over the past decade, including BRCA1 and BRCA2, two genes that have been shown to cause an inherited form of breast cancer. What's especially significant about DBC2 is that it appears to be involved in the more common forms of cancer that arise sporadically and without an inherited cause. Still, the Cold Spring Harbor Lab scientists say it isn't clear yet how often the damaged form of DBC2 is involved in typical breast cancer cases. |
|
|
| | 
Indeed, the scientists urge caution in interpreting how meaningful the DBC2 finding will be in the near term in the war against cancer. Over the years, scientists have learned that turning a gene discovery into new a diagnostic test or drug isn't a simple exercise. Dr. Hamaguchi says it will take much more research just to figure out what DBC2 actually does inside normal cells, to map the pathway it is part of, and to determine whether DBC2 is simply being damaged by a defect in some other, even more important, gene.
A more immediate result of the finding, Dr. Wigler says, may be that
doctors will be able to start categorizing breast cancer cells by their gene
defects. Certain tumors with a DBC2 defect, for instance, may be more likely
to respond to some therapies, while tumors with other defects may respond
better to other treatments. A full map of all the gene defects, it is hoped,
will produce a treatment guidepost that currently does not exist for cancer
doctors and their patients. | |
| Mary-Claire King, whose research led to the discoveries of BRCA1 and 2, says the newest finding is important because it proves the power of the cancer-gene mapping techniques being pioneered by Dr. Wigler and his labs. "Mike [Wigler] has developed a beautiful technology that allows researchers to identify many cancer gene candidates much more quickly than ever before," says Dr. King, who runs a gene-hunting lab at University of Washington, Seattle. "The goal of this approach is to produce someday a complete map of the differences, at the genetic level, between a cancer cell and a normal cell."
Dr. King is one of several co-authors of the research paper describing
the DBC2 gene that will be published next week in the Proceedings of the
National Academy of Sciences. |
|
|
| |  Dr. Wigler and his colleagues have developed a powerful set of laboratory tools that scan for meaningful differences in the DNA of normal and cancerous cells. Beginning in 1997, using this technique, Dr. Hamaguchi identified a region in chromosome 8 where the DNA in breast cancer cells appeared abnormal. By 1999, the lab had uncovered several genes in the region that, when altered in some deleterious manner, might spur tumor growth. One of the genes in the region was the one later to be named. "It hadn't been seen before in humans and its role in human biology was unknown," Dr. Hamaguchi says.
In order to determine whether DBC2 or the other genes in the affected
region might play a significant role in breast cancer, the scientists spent
18 months testing cancer cells to see if defective versions of the gene were
present in tumors but not in healthy tissue. In the scientific paper coming
out next week, the researchers report that DBC2 was abnormal in 11 of 18
lines of breast cancer cells it tested. In all 13 normal breast cell lines
examined the gene was working properly. Later, after testing other types
of cancer cells, the researchers found that DBC2 may play a role in lung
cancer, too, as the gene appeared to be defective in half of 14 lung cancer
cell lines while it was functioning in all 13 healthy lung cell lines tested. | |
| Cells use genes, like DBC2, to produce the numerous proteins that carry out most of the activities within a cell by interacting with one another in a series of events often described as a "biochemical pathway." The researchers believe that when DBC2 isn't working properly, it doesn't produce its protein, or it does produce it but in a defective form. Somehow this aberration helps create a pathway that isn't present in healthy cells, but is implicated in some cancers. The DBC2 gene and other gene discoveries like it may someday produce a complete map of all the pathways that spur cancer.
In an especially powerful experiment described in the PNAS research paper, Dr. Hamaguchi's lab produced further evidence suggesting that normal versions of DBC2 keep some breast and lung cells from becoming cancerous. The researchers implanted working versions of the DBC2 protein into cancer cells containing a defective version of the gene. With the protein inside, the cancer cells stopped multiplying and began behaving more normally.
Meanwhile, Dr. Wigler says, his lab expects soon to publish another paper describing a newer technique that he is convinced will shorten the time it takes to identify cancer-causing genes in a wide range of tumors. Still, he adds, "we have a long, long way to go before we really understand at the genetic level what is going on."
Copyright © 2002 Dow Jones & Company, Inc.
All Rights Reserved.
| |
|
MSNBC Interactive
Stocks suffer late-session slide
MSNBC's Health Library
MSN Health
