Discovery could lead to new targeted, individualized treatments, experts say
Researchers have identified 26 genes associated with the most common type of lung cancer, adenocarcinoma -- more than doubling the number of genes known to play a role in the deadly disease.The discovery could help in developing individualized ways of diagnosing and treating lung cancer, the top cancer killer, the researchers said.
"Although similar, smaller cancer gene sequencing projects have been reported, our study is the largest to date and provides the statistical power to detect significantly mutated genes," study co-author Richard Wilson, director of Washington University's Genome Sequencing Center in St. Louis, said during a Tuesday teleconference.
The research, known as the Tumor Sequencing Project, has important implications for the understanding, diagnosis and treatment of lung cancer, Wilson said. "But we consider it just a beginning. Over the next few years, we expect to extend this study both in terms of the number of individual cases that we study and the extent of the cancer genome we can explore," he said.
Before the new research, 10 genes linked to adenocarcinoma had been identified, including six of the 26 reported in this study. The findings were published in the Oct. 23 issue of Nature.
For the study, researchers looked for genetic mutations in lung cancer cells. These changes occur in the tumor and are not inherited or found elsewhere in the body, Dr. Matthew Meyerson, from the Broad Institute of MIT and Harvard and an associate professor at the Dana-Farber Cancer Institute in Boston, said during the teleconference.
"These mutations are important, because mutated genes can be targets for anti-cancer therapy," Meyerson said.
The researchers determined the DNA sequence of 623 genes in 188 lung adenocarcinomas. Then they compared the DNA sequence of these genes with the same genes in normal tissue from the same patients.
"By doing this, we identified 26 genes that are frequently mutated in lung adenocarcinoma," Meyerson said. "Most of these gene mutations are newly discovered."
Some of these genes have been implicated in other cancers, such as colon cancer, leukemia and lymphoma. "These genes could soon be new targets for lung cancer treatments," Meyerson said.
The researchers also looked at genetic mutations found among different adenocarcinoma patients. Most cases of lung cancer (90 percent) occur in smokers. Among smokers, there were many more gene mutations than those found in the lung cancer tumors of nonsmokers.
Tumors for smokers had as many as 49 mutations, while none of the nonsmokers had more than five mutations, the researchers reported.
"Our study could achieve a real impact on the care of lung cancer patients," Meyerson said. "It is important to study the role of the mutated genes in the growth and survival of lung cancer cells, which will help us work toward new treatments."
Dr. Norman H. Edelman, chief medical officer of the American Lung Association, called the new research another positive step in understanding cancer and could lead to new therapies.
"The methods of this study are powerful, and the sample is large, thus it is a good study. We can expect more like this," Edelman said. "The genetic basis of cancer is very complex, and this represents another piece of the puzzle. Whether or not finding newly implicated genes will lead to new therapies, as the authors suggest, is, of course, something to be hoped and waited for."
Lung cancer is the leading cause of cancer deaths in the United States and around the world. More than 1 million people worldwide die of lung cancer each year, including more than 160,000 people in the United States. Lung adenocarcinoma, the most frequently diagnosed form of lung cancer, has an average five-year survival rate of just 15 percent, the researchers said.
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