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Study finds new genetic error in some lung cancers
Date:10/28/2013

BOSTON 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 in the journal 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 (a form of non-small cell lung cancer), and that drugs that target NTRK1's protein product could be effective in patients whose lung tumors harbor such fusions.

"Treatment with targeted therapies is now superior to standard chemotherapy for many patients with lung cancers that harbor genetic changes including those with fusions involving the gene ALK," says Pasi A. Jnne, MD, PhD, of Dana-Farber, the senior co-author of the paper with Robert C. Doebele, MD, PhD, of CU Cancer Center. "We know of several other genes that are fused in lung cancer and that offer attractive targets for new therapies. Our discovery places lung adenocarcinomas with NTRK1 fusions squarely within that group."

In the study, researchers performed next-generation DNA sequencing tests which read the individual elements of the genetic code over long stretches of chromosomes on tumor samples from 36 patients with lung adenocarcinomas whose tumors did not contain any previously known genetic alterations that could be found with standard clinical tests. In two of those samples both from women who had never smoked investigators found that a key region of the NTRK1 gene had become fused to normally distant genes (to the gene MPRIP in one patient; and the gene 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 cell
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Contact: Robbin Ray
robbin_ray@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert  

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