How Genes' Behavior Affects Malignant Cells.

• Position: Brief Article

By looking at which genes are switched on and off in a variety of cancers, Stanford (Calif.) University Medical Center researchers are learning what thousands of genes do and why their behavior changes in malignant cells. Using the so-called DNA chip, they can study tens of thousands of genes at the same time and see how they vary in different tissues and how they respond to different drugs.

Scientists in the laboratories of Patrick Brown, associate professor in biochemistry, and David Botstein, professor of genetics, have mastered applying thousands of genes to a small piece of glass and deciphering the patterns that appear when they expose them to genetic material from human cells. Fluorescent tags make the genes glow red when they are highly active and green when they are idle. A computer program then sorts the genes into color patterns that can be interpreted by the researchers.

Doug Ross, a postdoctoral fellow in Brown's laboratory, examined 8,000 human genes in 60 different cancers including leukemia; cancers of the central nervous system; renal cell and non-small-cell lung carcinoma; melanoma; and ovarian, breast, colon, and prostate cancer. Cells from these cancers have been cultivated in the laboratory and comprise a cell panel constructed by the National Cancer Institute (NCI) in order to test new anti-cancer drugs.

Scientists already understand what some of the genes on the chip do. However, approximately half of them merely have a name or code number, and their function is unknown. When Ross and his colleagues analyzed groups of genes that are switched on or off in a similar way, they found that they often contained a mixture of known and unknown genes. The researchers assume that genes regulated in the same way have similar jobs, which enables them tentatively to assign functions to the unknown genes.

The researchers saw many complex patterns of gene expression among the cells, but it was clear to them that the predominant one corresponded to the tissue from which the cancer originally derived, For example, a large group of...