Unraveling the genetic picture of lung cancer

October 22, 2008

HOUSTON -- (Oct. 23, 2008) -- A study seeking possible cancer genes elucidated the mutations and the genetic pathways activated in the most common form of lung cancer - lung adenocarcinoma - and could lead to improved diagnosis and treatment, said the director of the Baylor College of Medicine Human Genome Sequencing Center that played a major role in the project led by the National Human Genome Research Institute.

In the report that appears in the Oct. 23 issue of the journal Nature, a national consortium of researchers called the Tumor Sequencing Project identified 26 genes that play a significant role in the development of lung adenocarcinoma as well as cellular pathways involved in the lung cancer. The analysis, involving 188 patients, more than any previous study, allowed scientists to find mutations associated with sub-types of the lung cancer - such as those among non-smokers.

Lung adenocarcinoma kills an estimated 1 million people worldwide each year. As many as 10 percent of people with the disease are non-smokers. It is one of the deadliest cancers in men and women with only about 15 percent of those whom it strikes surviving five years.

The findings highlight the complexity of the disease. Along with the work from other groups which included analysis of gene expression, the mutation study undertaken by the BCM genome sequencing center and colleagues promises to unlock many of the secrets of cancer itself.

"Clearly, much still remains to be discovered. We have just begun to realize the tremendous potential of large-scale, genomic studies to unravel the many mysteries of cancer," said Dr. Richard Gibbs, a co-author of the lung adenocarcinoma paper and director of the BCM Genome Sequencing Center.

In the study, members of the consortium sequenced key candidate genes from 188 tumor samples and matching non-cancerous tissue from the same person. This approach enabled the BCM researchers to identify mutations with unprecedented sensitivity. As a result, genes such as neurofibromatosis 1 and retinoblastoma 1, and several more that had been previously associated with other cancers, were discovered to be involved in this type of lung cancer.

"Our ability to detect cancer-causing genes with such great sensitivity enabled us to create the most comprehensive map ever of how this kind of tumor is able to defeat the body's defenses against cancer," said Dr. David Wheeler, an associate professor who led the BCM genome sequencing center analysis team. "These data are likely to have very near term impact on the way physicians think about treating lung cancer."

Some anti-cancer drugs used to treat other kinds of cancers may be useful in lung as well, the researchers noted.
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Others who took part in the study include scientists from the Broad Institute of MIT and Harvard in Boston, the Genome Center at Washington University School of Medicine in St. Louis, Brigham and Women's Hospital in Boston, Memorial Sloan-Kettering Cancer Center in New York, The University of Cologne in Germany, the University of Michigan at Ann Arbor and The University of Texas M.D. Anderson Cancer Center.

Funding for this work came from the National Human Genome Research Institute.

Once the embargo lifts, the full paper is available at www.nature.comFor more information on basic science at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.

Baylor College of Medicine

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