Scientists at Washington University School of Medicine in St. Louis, United States have identified 26 genes that that are frequently mutated in a common and deadly form of lung cancer, adenocarcinoma. Thus the number of genes known to play a role in the deadly disease has doubled.

"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 study on lung adenocarcinoma, also known as the Tumor Sequencing Project appears online Wednesday in Nature. But before the new research, 10 genes linked to adenocarcinoma had been identified, including six of the 26 reported in this study.
Lung cancer, the most common cause of cancer-related death in men and the second most common in women, is responsible for 1.3 million deaths worldwide annually. The most common symptoms are shortness of breath, coughing with or without blood and weight loss.

The scientists studied samples of lung adenocarcinoma donated by 188 patients from across the U.S., then worked through a catalogue of 623 "suspect" genes, many implicated in other cancers, comparing them in detail to the same genes in healthy tissue from the same patient. But apart from about 1,000 of other mutations the same 26 mutations were discovered to occur over and over again despite their never being linked to lung cancer before. The cross-linking genes include those that are common in colon cancer, types of leukaemia and lymphoma and a cancer of the nerve tissues called neurofibromastosis.

This is definitely a step towards developing new treatments that can be used on specific patients. For instance, the researchers discovered that more than 80 percent of the 188 tumours involved a mutation in a pathway called mitogen-activated protein kinase, or MAPK. Therefore drugs intended to specifically block the MAPK will be made. Moreover the finding that more than 30 percent of tumors had mutations affecting the rapamycin (mTOR) pathway raises the possibility that the drug rapamycin might be tested in lung adenocarcinoma.

Besides unveiling abnormalities within individual genes, the researchers uncovered extraordinary connections among them. By integrating DNA sequencing, gene expression, and DNA copy number data, they discovered that genetic aberrations are often localized to groups of genes that function together, relaying information from one part of the cell to another. All told, there are about 200 of these molecular circuits or "signaling pathways" that operate in human cells.

The study also confirmed previous observations that indicated lung cancer in never-smokers may be triggered by different genetic mutations than those in smokers. Smokers' cancers contained as many as 49 mutations, while non-smokers had five or fewer.
In order to convert the findings into treatments more rapidly, it will be important to understand what the findings tell us about genes that are mutated in metastases, an invasion of adjacent tissue and infiltration beyond the lungs.