Clinical Applications of Microarrays
Researchers at Roche Molecular Systems (www.roche-diagnostics.com) are developing several microarray technologies for clinical applications, including genotyping, re-sequencing, and gene-expression studies of disease tissue.
The AmpliChip CYP450 is a genotyping test for drug metabolism variations that impact individuals responses to approximately 20% of drugs on the market. The AmpliChip CYP450 test has applications in coronary arterial disease, psychiatry, and potentially in cancer, asserts Walter Koch, Ph.D, vp, head of research.
One of the genes we tested, CYP2D6, has its enzyme activity lacking in about 7% of all Caucasians because theyve inherited two nonfunctional alleles from their parents. Dr. Koch explains that if a breast cancer patient lacks this enzyme, she wont benefit from Tamoxifen because the CYP2D6 gene catalyzes its activation. In addition, many antidepressants and anti-psychotics are substrates for this enzyme.
However, Dr. Koch says in this case there are more apt to be adverse reactions to the medications. This gene is also important for other agents, such as beta-blockers, anti-arrhythmics, and common pain medications like codeine.
Another application being developed determines the sequence of the most frequently mutated gene in cancer, the P53 tumor suppressor gene. This is a slightly different use, instead of looking for variation distributed across a couple of genes, now were determining the exact sequence of the entire gene, Dr. Koch notes.
P53 is a master regulator of cell biology. It turns out that when the gene is mutated the protein isnt functioning normally, and these mutations are associated with poor prognosis as the cells are often resistant to chemotherapy. This can be important in making decisions about what therapy to choose in a particular cancer or in some cases, even driving therapy to an earlier stage.
A third application is using gene-expression profiling to categorize or sub-divide leukemias into molecular subtypes, most of which have different associated prognostic outcomes. We see a host of other cancer diagnostics that will employ this approach, states Dr. Koch. We know that the specific program of genes that are up- and down-regulated within a tumor can be informative about the molecular etiology of that cancer and that it is associated with both prognosis and treatment decisions.