Genetically targeted therapy for lung cancer can make treatment much more effective, but identifying the specific gene fusions involved in the disease remains a challenge. This may be about to change: A new study by researchers at Fox Chase Cancer Center demonstrates that RNA next-generation sequencing (RNA-NGS) can offer results that are more accurate and comprehensive while using smaller tissue samples.
Although the test isn’t new, only recently has the technology improved to the point where it’s viable for clinical use, said corresponding author Shuanzeng “Sam” Wei, MD, PhD, an associate professor in the Department of Pathology and medical director of the Clinical Genomics Laboratory at Fox Chase. He said the findings provided further evidence to support updating clinical guidelines to recommend RNA-NGS testing for lung adenocarcinoma.
“The national guidelines right now don’t have a definitive recommendation for the use of RNA-NGS for detecting gene fusions,” said Wei, who conducted the study with colleagues in the Department of Pathology. “But now, our platform is much better than it was previously, and RNA-NGS is just much more sensitive.”
Lung adenocarcinoma is the most common form of lung cancer in the United States, representing about 40 percent of all cases. Fusion genes can play a major role in the development of the disease, and when they appear, they can be targeted with specific therapies.
Most current testing protocols, including FISH and PCR, only can test for one fusion gene at a time, with tests usually focusing on the most common candidates. However, RNA-NGS testing can search for as many as 507 fusion genes with a single test.
“Even if you don’t know the partner gene, you can still get a positive result,” Wei said.
In addition, RNA-NGS can deliver accurate results with just a tiny sample of cells drawn from a fine needle aspiration of the tumor. In contrast, conventional testing methods require a tissue biopsy—a much larger sample extracted through an invasive procedure.
“The benefit for the patient is that the operation is small and causes minimal injury compared to a core biopsy,” Wei said. For the study, researchers used RNA-NGS to analyze 120 lung adenocarcinoma tumor cytology samples. They then used traditional testing methods, including DNA-NGS, FISH, and chromosomal microarray analysis, to verify the results.
The RNA-NGS testing had an overall success rate of 93 percent at detecting gene fusion. The older testing methods were less accurate and sensitive. Of the 22 samples analyzed for fusion genes using FISH, half of the tests failed because the samples did not contain enough material. Some of the positive results detected by FISH turned out to be false positives.
Even though RNA-NGS testing is easier to use and more accurate than traditional methods, the technology is not yet widely accessible. Fox Chase has one of the few comprehensive platforms available for clinical use in the United States. However, Wei said he expects the test to become more common in the coming decade.
The researchers plan to continue refining the technology by gathering data on its use in testing for different types of cancers, including sarcomas.
The study, “Cell Block-Based RNA Next Generation Sequencing for Detection of Gene Fusions in Lung Adenocarcinoma: An Institutional Experience,” was published in Cytopathology. The gene fusions illustration in this article was selected as the cover feature for the journal.