A fine-grained scan of DNA in lung cancer cells has revealed a gene fusion—a forced merger of two normally separate genes—that spurs the cells to divide rapidly, scientists at Dana-Farber Cancer Institute and the University of Colorado Cancer Center report in a new paper published in Nature Medicine. Treating the cells with a compound that blocks a protein encoded by one of those genes, NTRK1, caused the cells to die. The finding suggests that the fusion of NTRK1 to other genes fuels the growth of some lung adenocarcinomas and that drugs that target NTRK1’s protein product could be effective in patients whose lung tumors harbor such fusions.
Researchers performed next-generation DNA sequencing tests on tumor samples from 36 patients with lung adenocarcinomas whose tumors did not contain any known genetic alterations that could be found with standard clinical tests. In two samples, investigators found that a key region of the NTRK1 gene had become fused to normally distant genes (MPRIP in one patient; CD74 in the other). 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 without being prompted by outside signals.
In the laboratory, investigators mixed NTRK1-inhibiting agents into lung adenocarcinoma cells harboring NTRK1 fusions. The result was a dampening of TRKA’s activity and the death of the cancer cells. Investigators then used fluorescence in situ hybridization to detect NTRK1 fusions and tested 56 more tumor samples. In total, three of 91 samples with no other sign of cancer-causing genetic abnormalities had fusions involving NTRK1. Read the study abstract.