RNA-based testing can improve diagnosis and inform treatment of non-small cell lung cancer (NSCLC) caused by genetic mutations in the MET exon 14 splice region. That’s according to the paper, “Pitfalls in Detecting MET Exon 14 Skipping Variants by DNA- and RNA-Based Next-Generation Sequencing Technologies in a Large Real-World Cohort and Results of the First Multinational External Quality Assessment Schemes,” published in The Journal of Molecular Diagnostics.
Lead investigator Carina Heydt, PhD, said the research revealed the significant diversity of genomic alterations (171 in total) that can cause MET exon 14 skipping and indicated that these can be missed or interpreted incorrectly by DNA-only testing approaches.
“Although MET exon 14 is a well-established predictive biomarker, our findings highlighted a level of molecular complexity that is often underappreciated in routine diagnostic practice,” said Dr. Heydt in an Elsevier press release.
The study included 379 samples from patients with NSCLC. Researchers were able to analyze 114 mutations of the 171 represented using RNA- and DNA-based next-generation sequencing (NGS) assays. RNA-based NGS detected two large deletions and one synonymous splice variant that were not detected with DNA-based assay.
The laboratory performance through external quality assessment schemes had a 98% overall success rate, while the liquid biopsy tests had lower rates of 63% in 2024 and 37.5% in 2022.
Dr. Heydt said these findings are critical for clinicians to know if, when and how to use MET-targeted therapies.
“To improve diagnostic accuracy, incorporating RNA-based confirmation, where feasible, can improve sensitivity and specificity for identifying true exon-skipping events,” she said.
“This study highlights the importance of analyzing both DNA and RNA, urging improvements in sensitivity, coverage and bioinformatics,” the authors wrote.
