Chipping away at cancer
How gene microarrays or "gene chips" are transforming research
By Richard Saltus
No matter what causes it or where it starts, cancer is a disease that involves genes behaving badly. Smoking, radiation, chemical exposure, aging, or random bad luck can all lead to cancer, but they do so through damage to our 25,000 genes—the human genome.
It is not known how many abnormal genes ultimately lead to the misdeeds of cancer cells. Some become "oncogenes," spurring aggressive, uncontrolled cell growth. Conversely, damaged "tumor suppressor genes," which normally prevent the development of cancer, are like failed brakes on a car. Other genes signal cancer to progress, and contribute to resistance to drug therapy. Still others shield cancer cells from "programmed cell death," a natural process for eliminating unwanted cells.
Understandably, much of today's cancer research focuses on differences between genomes (the entire set of genes) of cancer cells and normal cells. Already, researchers have identified many individual and groups of genes that are busy making proteins in cancer cells but are silent in normal cells—and vice versa.
These differences in gene activity help scientists classify cancers in new ways, and give clues to the abnormal biology of cancer.
"In the past, we've identified tumors using a few individual genes," says Eric Winer, MD, director of the Breast Oncology Center within Dana-Farber's Women's Cancers Program (WCP). "With the new technology for surveying the genome of cancer cells, we can look at a few thousand genes at the same time. It is the difference between seeing just a person's eyes behind a mask and seeing the entire face."
Genomic surveys of cancer cells have identified a number of broken genes that can be targeted by designer cancer drugs that leave normal cells alone, since those cells don't contain the genetic flaws. Examples are drugs like Gleevec, Iressa, and Tarceva. Predictive tests such as Oncotype DX also take advantage of genomic technology. (For more details on the Oncotype DX test, see "Ask the Care Team")
Two landmark events in the past decade have opened a new window into the genetic underpinnings of cancer. First, the Human Genome Project yielded the "text" of the DNA sequences that spell out the operating instructions for our cells; it also produced a catalog of the collection of genes in human cells. The coded messages in the genes—recipes for making proteins that form the body's structure and regulate its function—contain many clues to the origin of cancers.
Second, biotech companies invented devices called gene microarrays, or "gene chips," that can survey the behavior of all the genes in a cell at once. A microarray is like a tiny laboratory on a silicon rectangle, or chip, the size of a postage stamp. Microarrays measure the activity or "expression" of the genes in the cell—that is, which ones are making RNA, the chemical required for the DNA blueprint of the gene to be translated into a protein.
The microarrays, or gene chips, are read by a scanner, which produces a torrent of mathematical data that a computer converts into vivid, colored displays of gene activity. The readout of which genes are turned off and turned on in a type of cell yields its specific "signature" or "fingerprint (See illustration, The power of gene chips)."
- Next: Tumors' gene "signatures"
- Page: 1 | 2 | 3 | Illustration: The power of gene chips
