Listening to genes
Cancer cells present their foes — in this case, scientific investigators — with a multitude of targets. Compare the pattern of gene activity in a cancer cell with that of a normal cell, and one is likely to find hundreds or even thousands of differences. How to determine which are important and which are trivial, which cause cells to become cancerous and which keep them that way?
Lynda Chin, MD,'s answer: Let cancer cells themselves provide the clues.
Chin and her Dana-Farber colleagues are conducting a high-speed search for sections of cancer cell chromosomes that are either missing or unusually long. Since genes reside on chromosomes, such abnormalities would point to genes that are absent from cancer cells or are copied over and over again like a molecular stutter.
Gene chips are helping Lynda Chin, MD, understand cancer.
"The fact that cancer cells have evolved this method of altering their genetic programming — deleting some portions of chromosomes and amplifying others — suggests that the genes within those portions are particularly important to the cancer process," Chin remarks. "Instead of scouring the entire genome for potential cancer genes, we can focus on the likeliest candidates."
To find abnormal stretches of chromosome, Chin and her associates have adapted microarray technology for a new purpose. Using palm-sized cartridges — or "chips" — embedded with genetic material, the investigators compare snippets of normal-cell chromosomes with their cancer-cell counterparts. When divergences are found, the researchers refer to the human genome map to determine the genes involved.
Because genes are often bunched closely together (hundreds can be strung along a short segment of chromosome), the challenge is to compare sections that are small enough to contain only a few. Chin's team has devised a method and analytical tools for doing that, and it has enabled the group to find previously unidentified genetic alterations in melanoma, pancreatic cancer, multiple myeloma, and breast and lung cancer cells.
"This technique has accelerated our ability to find genes with potential relevance for cancer, collapsing months or years into days of discovery," Chin says. "The sequencing of the genome provided the 'raw data' of genes' locations. We're now using that as a springboard for a more refined search."
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