By David N. Leff

A newly discovered gene is something like a new model automobile. Both are shrouded from view until the wraps come off at the moment of formal revelation. In the case of next year's car, dealers can't wait for the cover to be whisked away to prompt sales.

In the case of a novel gene, the "dealer" is the Securities and Exchange Commission, which expects a company that makes a signal discovery to come clean soonest, avoiding rumors on The Street that might kite its stock.

Thus, Myriad Genetics Inc., of Salt Lake City, and its research partner, the M. D. Anderson Cancer Center, in Houston, on Wednesday reported the identification of a brain cancer gene, minus publication in a peer-reviewed journal.

Myriad stock (NASDAQ:MYGN) gained $2.75 on the news Wednesday, to close at $33.25.

Its two principal investigators, molecular biologists Sean Taztigian, director of cancer research at Myriad, and Peter Steck, at M. D. Anderson, foresee that journal publication of their discovery of the first major glioma gene is still several months in the future.

Meanwhile, both their institutions will be filing a patent application "in the next two weeks," Taztigian told BioWorld Today, "with Steck and myself as lead inventors."

And "this week," he added, "we're going to be checking gene mutations in primary tumors in a lot of glioma cell lines."

Glioma, a form of brain tumor, is the leading killer of children with cancer. "Over 28,000 cases of it were diagnosed last year in the U.S.," said Steck. "What we're looking at is glioblastoma, the most malignant form, and also the most common."

Glioma Therapy Needs Work

"Surgery, radiation and chemotherapy," he observed, "now extend life, but are generally ineffective in the long term. In other words, the median two-year survival of glioblastoma is less than 5 percent."

Late last year, his group at M. D. Anderson's department of neuro-oncology found deletions in glioma cell lines that pointed out the region harboring the gene. Then he cloned a small part of the gene sequence, and turned it over to Myriad's Taztigian and his team, who completed mapping and sequencing it in December.

They found mutations in a half dozen of Steck's glioma cell lines, plus one, curiously, in a prostate cancer line. "Other than that this gene appears to be involved in both, I don't know of any connection," Taztigian said. "It's one of the things we're trying to find out right now. Here at Myriad," he continued, "we have a whole bunch of tumor cell lines from a wide variety of different cancers, and we're starting to mutation-screen them to figure out the variety of tumors that this gene is involved in."

The researchers have pinpointed the chromosome in the human genome on which their brain-cancer gene, BNC1, resides, as well as its probable function. But they decline to divulge this data, pending publication.

In general terms, Taztigian defines the action of the normal BNC1, gene: "We do have a clue," he said, "and of course we can't say at this point what we think it does, but this gene product, and another gene product that we have yet to identify, are going to form a mutually antagonistic pair."

He explained: "Meaning that they'll have biochemical functions; one does something, and the other undoes it."

If that "something" were, for example cell cycle progression, he suggested, using an unrelated analogy, "if you wanted to pharmacologically slow cell cycle progression by taking advantage of this antagonistic-pair system, you'd try to design a small molecule to inhibit the progression."

At Myriad, he allowed, "we have one of a pair of enzymes that should do this sort of thing. And we're going to look for the other one. When that's done, we'll have both a gene with potential value for gene therapy, and a gene that will give us an in to develop small molecules that will have an effect on the cancer phenotype of the cell."

But the Myriad scientist also made this point: "We're always working on developing relations with pharmaceutical companies. Myriad itself doesn't have the capacity * and isn't interested in developing the capacity * to find small-molecule drugs. We really want to focus on the positional cloning, and let the pharmaceutical companies do the drug discovery."

"From the pharmaceutical companies' point of view, one of the main advantages of finding out about an interesting gene from us is that it will be published in a little while, hopefully," he said. "That gives them a head start vs. the rest of the world, in addition to whatever patent rights we may end up with." *