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A multi-institution team, funded by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH), today reported results of the largest effort to date to chart the genetic changes involved in the most common form of lung cancer, lung adenocarcinoma. The findings should help pave the way for more individualized approaches for detecting and treating the nation's leading cause of cancer deaths.

In a paper published in the Oct. 23 issue of the journal Nature, the Tumor Sequencing Project (TSP) consortium identified 26 genes that are frequently mutated in lung adenocarcinoma - an achievement that more than doubles the number of genes known to be associated with the deadly disease. But the pioneering effort involved far more than just tallying up genes. Using a systematic, multi-disciplinary approach, the TSP team also detailed key pathways involved in the disease, and described patterns of genetic mutations among different subgroups of lung cancer patients, including smokers and never-smokers.

More than 1 million people worldwide die of lung cancer each year, including more than 150,000 in the United States. Lung adenocarcinoma is the most frequently diagnosed form of lung cancer. The average 5-year survival rate currently is about 15 percent, with survival being longest among people whose cancer has been detected early.

"By harnessing the power of genomic research, this pioneering work has painted the clearest and most complete portrait yet of lung cancer's molecular complexities. This big picture perspective will help to focus our research vision and speed our efforts to develop new strategies for disarming this common and devastating disease," said NHGRI Acting Director Alan E. Guttmacher, M.D.

Like most cancers, lung adenocarcinoma arises from changes that accumulate in people's DNA over the course of their lives. However, little is known about the precise nature of these DNA changes, how they occur and how they disrupt biological pathways to cause cancer's uncontrolled cell growth. To gain a more complete picture, researchers have joined together to form TSP and other large, collaborative projects that are using new tools and technologies to examine the complete set of DNA, or genome, found in various types of cancer.

"We found lung adenocarcinoma to be very diverse from a genetic standpoint. Our work uncovered many new targets for therapy of this deadly disease - oncogenes that drive particular forms of lung adenocarcinoma and tumor suppressor genes that would ordinarily prevent cancer cell growth," said Matthew Meyerson, M.D., Ph.D., a senior author of the paper. Dr. Meyerson is a senior associate member of the Broad Institute of MIT and Harvard and an associate professor at the Dana-Farber Cancer Institute and Harvard Medical School.

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