Scientists Close To Finding Gene That Controls Growth Of Lung Cancer

November 10, 1997

DURHAM, N.C. -- In what may move scientists a step closer to locating a gene that helps control the growth of lung cancer, researchers at Duke University Medical Center have found in a new study that fragments of a portion of a human chromosome slow tumor growth in mice and in cell cultures.

The strand of DNA that was the focus of the study was chromosome 11. The researchers said they believe a specific section of that chromosome contains a tumor suppressor gene that controls the spread of lung cancer.

The finding was published in the September/October issue of the international journal Anticancer Research.

"Whatever is in this region on chromosome 11 is able to change the growth and morphology of already formed cancers, and that's an important aspect of this study," said Dr. Gerold Bepler, associate professor of medicine at Duke and senior author of the report. "It means that, whatever is broken in that system, if you repair it, you may be able to change the biologic behavior of the existing cancers."

About 177,000 people in the United States are expected to be diagnosed with lung cancer this year, making it the leading cause of cancer death for men and women in the nation. More people die each year of lung cancer than of colon, breast, and prostate cancer combined, and annual treatment costs amount to about $5 billion, according to the American Cancer Society.

The research was supported by grants from the Jimmy V Foundation, the North Carolina Biotechnology Center, and the National Cancer Institute.

Bepler began looking at chromosome 11 as a possible location for a gene or genes that cause lung cancer several years ago. He and his colleagues had found that a large percentage of patients were missing a portion of chromosome 11. This region is called LOH11A and is associated with the spread of tumor cells. Therefore, he said, that segment of chromosome 11 probably contains a gene that controls the aggressiveness of lung cancer.

The scientists were looking for tumor suppressor genes, which play a key role in whether a patient gets cancer. Tumor suppressor genes are normal genes that act to inhibit the formation of cancerous cells, but if the genes become mutated and are unable to do their job, there is nothing to stop the tumor from growing.

In this study, the researchers took a normal segment from the LOH11A region and inserted it into tumors that were then studied in mice and in liquid cell cultures in laboratory dishes.

They found that half of the tumors did not grow at all, and half demonstrated greatly suppressed growth. They used chromosome 12 as a control, since it has not been implicated in lung cancer, and found that the tumors injected with the control chromosome grew at the usual rate. As a result, they believe that a tumor suppressor gene may be within the LOH11A region of chromosome 11.

Bepler, who also serves as chief of hematology/oncology services at the Veterans Administration Medical Center in Durham, said the discovery "provides further confirmation that a tumor suppressor gene is located in LOH11A on chromosome 11. If you put this piece of chromosome 11 back into a cancer cell line, it grows much more slowly, if at all."

He said the study is "an entirely different approach" to finding the tumor suppressor gene that causes lung cancer than previously taken by his group. In the past, the researchers focused on DNA at the molecular level, whereas the new study takes a biological approach, looking at the tumors themselves.

Bepler and his colleagues hope their work could eventually lead to new treatments for lung cancer patients after further study and refinement. The pieces of chromosome used in this study are too large to insert into tumors in patients, he said. That's why it's important to find the gene itself, which is small enough to be injected into the tumor cells without being rejected.

Currently, lung cancer is treated with surgery in the early stages, or surgery combined with radiation therapy and chemotherapy in the advanced stages. About 75 percent of patients who have surgery in the early stages will eventually have recurrent disease. The five-year survival rate for all stages is 14 percent. Symptoms often do not appear until the disease has advanced, so early detection is difficult.

Bepler said the next step is to find the tumor suppressor gene, and his team continues to search for a gene or genes responsible for the disease.

Other authors of the paper were Kathy O'Briant, Ethel Jolicoeur, Jennifer Garst, Mike Campa, and Gilbert Schreiber, all of Duke.

Duke University Medical Center

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