Zhou Y, et al. - This study was performed to characterize squamous cell carcinomas (SCCs) based on NTRK2 gene expression using the accuracy of RNA measurement, and to develop a reproducible method to identify aggressive tumors. Researchers here exclusively focused on measuring the two most common forms of NTRK2 gene RNAs: TrkB-FL and TrkB-T1. According to the expression of a single form of NTRK2 mRNA, TrkB-T1, identified by its unique 3′ terminal exon, they classified the tumors from the Cancer Genome Atlas (TCGA) and other studies. They analyzed differentially expressed genes in TrkB-T1 high expressers to determine if tumors enriched for TrkB-T1 mRNA were a uniform group independent of anatomic site. In all SCCs in the TCGA database, the mRNA for TrkB-T1 is the most abundant NTRK2 gene mRNA. Findings indicated SCC anatomic site-specific relationship of high-level TrkB-T1 expression to patient outcomes. In laryngeal SCC, they observed poor survival in correlation to high TrkB-T1 mRNA levels, however, they noted opposite as true for lung SCC. Findings suggest the value of high-level TrkB-T1 mRNA as a marker of a distinct SCC subtype enriched for at least three pathways related to tumor progression: Nfe2l2 response, retinol metabolism, and hedgehog signaling.