Researchers Identify New Genetic Error in Some Lung Cancers

Researchers have identified examples of gene fusion in lung cancer cells, suggesting a previously unknown cause of a disease responsible for killing more than 160,000 people living in the United States every year.

Gene fusion refers to a process in which two separate genes merge, causing the cell to divide quickly. According to the study published in the journal Nature Medicine, treating the cells with a compound that blocks a protein encoded by one of those genes, known as NTRK1, kills them.

The researchers, from the Dana-Farber Cancer Institute and the University of Colorado Cancer Center, ran DNA sequencing tests on tumor samples from 36 patients. Each sample was void of any previously known genetic alteration. In two of them, both of which came from women who had never smoked, a key region of the NTRK1 gene had fused to normally distant genes.

According to the press release outlining the discovery, "NTRK1 holds the blueprint for a protein called TRKA, which dangles from the surface of cells and receives growth signals from other cells. The binding of NTRK1 to other genes causes TRKA to issue cell-growth orders on its own, without being prompted by outside signals."

Back in the lab, the researchers mixed NTRK1-inhibiting agents into lung cells containing NTRK1-fusions. Doing so dampened TRKA activity and killed the cancer cells.

They then created a new test to detect NTRK1 fusion and tested 56 tumor samples. In all, three of 91 tumor samples containing no other sign of cancer-causing genetic abnormalities contained fusions involving NTRK1.

"These findings suggest that in a few percent of lung adenocarcinoma patients -- people in whose cancer cells we had previously been able to find no genetic abnormality -- tumor growth is driven by a fusion involving NTRK1," said senior co-author Dr. Pasi A. Jänne. "Given that lung cancer is a common cancer, even a few percent is significant and translates into a large number of patients. Our findings suggest that targeted therapies may be effective for this subset of lung cancer patients."