Colon Cancer Gene Discovered

Scientists and cancer advocates are hopeful that the isolation of the gene which causes an inherited form of colon cancer, announced by Medical School researchers last week, will increase the survival rate of those in danger of contracting the disease.

The identification of the gene which causes hereditary nonpolyposis colorectal cancer, an inherited form of colon cancer, should enable doctors to screen patients before any tumor growth in order to determine whether they are predisposed to contract the disease.

More than a million Americans are thought to carry the gene for this type of cancer, which accounts for 10 to 15 percent of all cases of the disease.

The findings were published last Friday in Cell by the study's principal authors, Dr. Richard D. Kolodner, professor of biological chemistry and molecular pharmacology at the Medical School and Dr. Richard Fishel of the University of Vermont. A follow-up article will be published by scientists at the Johns Hopkins Oncology Center within two weeks.

"It's an important step," says Deb Beatty Mel, a spokesperson for the American Cancer Society's Boston division.

The speed with which the nature of the gene was confirmed will facilitate patient screening, the next step in disease prevention.

According to Medical School Assistant Professor of Medicine Dr. Judy E. Garber, director of the cancer risk and prevention program at the Dana Farber Cancer Institute, screening will begin with tests for the gene in the healthy relatives of colon cancer patients.

Once identified, those who do carry the gene will be carefully monitored so that any tumor which begins to grow may be detected early.

Kolodner says that many patients who may not have otherwise survived will be cured by this approach.

"The prospects [for survival] are actually pretty good," he said. "In cancer early detection is very important. If you know who to follow you can easily find the very earliest stages, operate, and people are essentially disease-free."

The discovery has received particular attention in scientific circles because it was unanticipated--and came about as a result of basic genetic research not directed specifically at colon cancer.

"It's evidence that basic science leads to important advances in cancer control," says the Cancer Society's Mel.

Kolodner describes the fortuitous events which led to the discovery as "an interesting scientific story."

Although his research focuses on increased rates of mutation, or changes in the sequence of DNA, in yeast, it had occurred to Kolodner that mutants in human cells which correspond to the yeast mutants he was studying might be instrumental in causing diseases.

His hunch was confirmed with the publication this summer of several scientific journal articles. According to the articles, tumor cells from patients with the inherited form of colon cancer bore a base pair sequence similar to that carried by the yeast mutants he was studying.

Intrigued, Kolodner's research group sequenced the mutations and found that they lay in the region of chromosome 2 known to be involved in colon cancer.

The fact that information on the function of the gene, involved in DNA proofreading, is known from past studies of Kolodner's yeast system should mean that future research will move forward that much more quickly, scientists say.