DNA Microarrays: A New Tool for Cancer Diagnosis

Predicting the course of the disease for a person diagnosed with cancer can often be puzzling. A definitive diagnosis for cancer involves taking a biopsy of a tumor or a suspected tissue in the body, and examining the cells under a microscope. Cancer cells can vary from being quite similar to normal cells in appearance to being totally without structure and organization. Physicians use this histopathological examination to determine the prognosis, or the prospect for the patient's recovery from the disease. However, appearances can be deceiving. A treatment that cures one cancer can fail against its identical looking pair.

A new technology is rapidly being developed that promises to revolutionize the classification and diagnosis of cancers, as well as to provide a sounder basis for deciding on a course of treatment. The new technology classifies tumors by molecular characteristics, rather than by cell features. Patrick Brown and associates of the Stanford University College of Medicine developed this technology, known as DNA microarrays or DNA chips. The procedure determines which genes among thousands tested are active, and allows researchers to prepare unique gene expression profiles for different types of cells. Eric Lander and Todd Golub of the Whitehead Institute in Cambridge used the procedure to identify examples of inappropriate gene expression in cancers. Fortunately, this has come at a time when a vast amount of genetic information is coming out of the Human Genome Project. Last year, the National Cancer Institute launched a major effort to compile a comprehensive record of all the genes involved in human cancer.

A DNA microarray can be thought of as analogous to a computer chip, but instead of containing electronic circuits, the chip contains thousands of minute cells. To create a microarray, robotics place tiny droplets containing gene fragments on specific locations on a glass slide. In the case of cancer, the gene fragments could come from those genes that were determined to be involved in cancer. In order to diagnose a cancer, the suspect tumor or tissue is biopsied, and messenger RNA extracted from the cells. The rationale behind this procedure is that when genes become active, its DNA code is transferred to messenger RNA. The messenger RNA sequences are then copied onto corresponding sequences of the more stable complimentary DNA. The complimentary DNA is then labeled with fluorescent dyes, and added to the gene fragments on the slide. If the gene is active, its labeled DNA will bind to the gene fragment, and produce a brighter color. A scanning microscope measures the intensity of the spots, and the results are recorded on a graph. Computer programs then sort out the raw data in order to determine distinctive signatures of gene expression in the biopsied sample. 2 3 5.

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