Science writers have expended a great many words on “gene chips,” which are being touted as biological crystal balls that will diagnose future genetic susceptibility to disease. Having contributed my share of adjectives to this futuristic vision, I know how tempting it is to describe.
But technologies often travel the low road to widespread use, and while prognostic gene chips may well be a routine feature of annual physical checkups in the future, a related chip application has already entered the clinic through the back door. “Molecular profiling” is one name this technology goes by, and these highly precise genetic tests do not exactly predict the future. Rather, these chips assess the molecular stage of a patient’s disease, and may ultimately suggest which drugs the patient might respond to.
It takes a genetic disease to beget a genetic test, and one of the most inviting targets-for marketing as well as molecular reasons-is a tumor-suppressor gene known as p53. Even in this frenzied “Gene-of-the-Week” era of biological discovery, p53 is a legitimate cover boy for the genetics of cancer, having earned the appellation of “Molecule of the Year” from the journal Science in 1993 and later appearing on the cover of Newsweek.
The reason for this celebrity is that the p53 gene, in its normal and intact state, plays the bouncer inside the velvet rope of a cell, mindful of the slightest aberrant behavior, such as the unchecked replication typical of cancer cells. The gene essentially orders a disobedient cell to commit suicide, which is an excellent biological way to suppress the rise of incipient tumors. Tumor cells grow better when p53 is inactivated by mutations, so there is strong Darwinian selection for cancer cells that shut off p53. Indeed, fully 50 percent of all human cancers are marked by disabled p53 function, including major killers like lung, breast, and colon.
Given its importance, clinicians would like to know the p53 status of every tumor they’re trying to treat. About two years ago, biochip-maker Affymetrix joined forces with Oncormed, a cancer diagnostics company based in Gaithersburg, Md., to make p53 testing one of the prototypes of chip technology. Their target: the coding region of the human p53 gene, which possesses 1,262 base pairs of DNA-the chemical subunits of the double helix that tell a cell how to make the p53 protein.