Genetic Test For Melanoma Developed At UCSF

The test, which detects chromosomal abnormalities that characterize cancerousskin cells, was described here, today (March 9), at the annual meeting of theInternational Society of Dermatopathology.

A skin mole that looks suspicious to a dermatologist is usually biopsied andexamined under the microscope. But even with years of experience it'ssometimes impossible to make a clear decision as to whether or not the mole iscancerous. And sadly, many melanoma cases slip through the screening process;according to some insurance carriers, these cases account for six percent ofthe money awarded each year in malpractice suits.

Because melanoma results when a cell's genetic machinery gets out of control,Philip LeBoit, MD, a professor of pathology at UCSF, and his colleagues begancomparing chromosomes of normal skin cells with those of cancerous ones. In atest called comparative genomic hybridization, they labeled DNA from normal andcancerous cells with different fluorescent dyes, then used these to identifythe changes in the cancer cell's chromosomes.

These experiments were conducted by Boris Bastian, MD, an assistant professorof dermatology, Dan Pinkel, PhD, a professor at the NCI-designated UCSFComprehensive Cancer Center, and LeBoit.

Clear patterns have emerged in the first 100 cases that LeBoit and hiscolleagues have studied: 82 percent of melanoma tumors lack portions of the DNAnormally found on one arm of chromosome 9, 63 percent are missing sections ofchromosome 10, and 50 percent of tumors have extra DNA on chromosome 7. Cancercells that are missing DNA have shut down certain genes on that chromosome and,similarly, extra DNA suggests that the melanoma has generated extra copies ofsome genes on that chromosome.

By testing suspicious looking skin cells for these abnormalities,dermatologists can be much more certain of their diagnoses, LeBoit said. "Nowwe have a common set of abnormalities for melanoma. And most tumors have two,three or four of them," he said.

Before pathology labs around the country can begin using the test, it needs tobe simplified, LeBoit said. "It now takes a more sophisticated molecularbiology lab and weeks to months of work to get an answer for a given case," hesaid. The experimental version of the test will be replaced by one that usesfluorescent markers to light up the aberrant chromosomal regions in tumorcells. "This type of fluorescent test is much easier to do technically," hesaid.

The chromosomal tests should also help when a melanoma is discovered, byshowing where the cancer stops and the normal cells begin. This will enabledermatologists to cut out only the cancerous cells and leave behind the healthyones, LeBoit said.