In addition, the genetic findings suggest that certain lung cancer patients might benefit from chemotherapy drugs currently used to treat other types of cancer. For example, chemotherapy drugs known to inhibit the kinase insert domain receptor (KDR), such as sorafenib and sunitinib, might be tested in the relatively small percentage of lung adenocarcinoma patients whose tumors have mutations that activate the KDR gene.

In their Nature paper, TSP researchers also analyzed the patterns of genetic changes seen among different subgroups of lung adenocarcinoma patients, including smokers.


About 90 percent of lung cancer patients have significant histories of cigarette smoking, but 10 percent report no use of tobacco. In the TSP study, the number of genetic mutations detected in tumor samples from smokers was significantly higher than in tumors from never-smokers. Smokers' tumors contained as many as 49 mutations, while none of the never-smokers' tumors had more than five mutations. More work is needed to determine what these differences may mean for the management of lung cancer. However, doctors do know that in some other types of cancer, high mutation levels may cause a tumor to spread rapidly and/or be resistant to treatment.

"Our findings underscore the value of systematic, large-scale studies for exploring cancer. We now must move forward to apply this approach to even larger groups of samples and a wider range of cancers," said Richard K. Wilson, Ph.D., a senior author of the paper and director of the Genome Sequencing Center at Washington University School of Medicine, St. Louis.

The TSP team also included researchers from Baylor College of Medicine, Houston; Brigham and Women's Hospital, Boston; Memorial Sloan-Kettering Cancer Center, New York; the University of Cologne, Germany; the University of Michigan, Ann Arbor; and the University of Texas M.D. Anderson Cancer Center, Houston.

"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 Richard Gibbs, Ph.D., a co-author of the lung adenocarcinoma paper and director of the Human Genome Sequencing Center at Baylor College of Medicine.

The TSP data are complementary to those from other large-scale cancer genome studies, such as The Cancer Genome Atlas (TCGA) project funded by NHGRI and the National Cancer Institute (NCI). In its pilot phase, TCGA is focusing on the most common form of brain tumor, called glioblastoma; a type of lung cancer called squamous cell lung cancer; and ovarian cancer. The first results from TCGA's glioblastoma study were published in the advance online edition of Nature on Sept. 4 and published in Nature's print edition on Oct. 23.

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