Patients whose tumors contained a large number of gene fusions had worse outcomes than patients with fewer gene fusions, according to researchers at the University of Michigan Comprehensive Cancer Center who analyzed the DNA and RNA of lung cancers. Gene fusions are a type of genetic anomaly found in cancers that occurs when genes get rearranged and fuse together. Researchers also identified several new genetic anomalies that occur in lung cancer, including in patients with a history of smoking.
Study author Arul Chinnaiyan said, "Lung cancer is quite a complex disease with many causes. Our deep sequencing analysis found new gene fusions in lung cancers that were negative for the most commonly known fusions. These new anomalies could potentially be targets for developing new treatments."
Researchers studied 753 lung cancer samples that represented both smokers and non-smokers. They found 6,348 unique fusions with an average of 13 fusions per tumor sample. Anomalies in two gene pathways were most prevalent- the Hippo pathway, which has previously been linked to some rare cancers; and NRG1, which has not previously been linked to cancer. The researchers recommend expanding lung cancer subtypes based on these molecular characteristics.
The team suggests exploring these inhibitors as potential therapeutics in lung cancer. Pharmaceutical companies are already investigating drugs that could target the Hippo pathway and NRG1. Also, the finding that the number of gene fusions was linked to prognosis suggests that a screen could be developed to help doctors determine how aggressive a patient's tumor is likely to be and to personalize treatment accordingly.
The study is published in 'Nature Communications'.