ABOUT THE COVER
The Xp11.2 chromosomal translocation underlies a subgroup of aggressive renal cell carcinomas (TFE3-RCC) with distinct molecular and histological features. These tumors are driven by a pathogenic chimeric form of the TFE3 transcription factor, but diagnostic and therapeutic options for TFE3-RCC are limited. Using a novel transgenic mouse model, the authors found that RET kinase expression was upregulated in mouse kidney tumors with chimeric TFE3 signaling, and TFE3-RCC mouse tumors demonstrated a therapeutic response to the RET inhibitor vandetanib. As shown in a representative section on the cover, immunohistochemical staining for RET was also positive in human kidney tumors from patients with TFE3-RCC. Additionally, the authors identified Glycoprotein Nonmetastatic B (GPNMB) as a novel biomarker of TFE3-RCC that outperformed the conventional marker, Cathepsin K. These findings expand the potential diagnostic and therapeutic options for TFE3-RCC, and present a novel mouse model for further preclinical investigation. See the article by Baba et al. on page 1613 for more information.