A rapid, inexpensive, precise test to determine a person'slikelihood of getting cancer some day is "on the brink ofseeking a commercial outlet," said the director of MassachusettsGeneral Hospital's Cancer Center, Kurt J. Isselbacher.

He told BioWorld that the hospital has filed for patentprotection of the methodology, so "I think it's ready to beapplied."

Isselbacher emphasizes that "clearly, currently it is still aresearch tool, and ideally it should be done commercially. Wehave had a number of discussions with industry, but withnothing agreed to yet."

The new and improved assay of genetic susceptibility to canceris based on a peculiar, 393-amino-acid, 53-kiloDaltonphosphoprotein named "p53." It is encoded by the white-hat/black-hat p53 gene, which is located on humanchromosome 17. In its benign guise, native p53 acts as atumor-suppresser gene, blocking runaway DNA fromtranscribing and replicating malignant cells.

In its oncogenic disguise, mutant p53 synthesizes a tumor-promoting protein, which turns up in all of the cells of mostcancer patients.

A team of molecular oncologists at the MGH Cancer Centerannounced Tuesday in the journal Cancer Research that theyhave developed a novel method for revealing these cancer-causing germline mutations in the DNA of p53. They check outthe unnatural protein it makes rather than analyze the mutantgene sequence.

Stephen H. Friend, lead author of the paper that reported thenew screening technique, finds this approach -- looking atprotein rather than gene -- "powerful and intriguing on aconceptual as well as a practical level."

Once in use, the method will potentially permit screening oflarge, healthy populations of people to identify individualswhose cell nuclei harbor a crippled p53 protein. Finding such agermline mutant would signal that the individual tested had amuch higher than normal genetic susceptibility to cancer, andsuggest an intensified diagnostic effort -- such as earlier andmore frequent mammograms -- and more aggressive therapy ifand when a malignancy actually came to light.

A woman found carrying the flawed p53 gene, and hencetumor-prone, might request prenatal diagnosis when pregnantto avoid passing the inborn genetic error to her child.

Current laboratory procedures scan the p53 gene sequence formutant bases one nucleotide at a time, a tedious, complicatedtask that can take a week to a month.

Since submitting his paper to Cancer Research in early October,Friend told BioWorld, his group has been further simplifying itsprototype rapid assay. The researchers are now aiming to carryout this assay in a yeast expression system. This would entailcombining the previous two-step operation of first cloning avector, then transfecting the host cell. The resultant geneproduct is finally incubated with the individual's fibroblastsand lymphocytes to see if they function in activating DNAtranscription as potential tumor suppressers or promoters: ablue plaque in a petri dish, or a colorless one.

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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