Caliò A, et al. - Researchers determined vascular endothelial growth factor A (VEGFA) amplification by fluorescent in situ hybridization (FISH) and VEGFA mRNA expression by in situ hybridization (RNAscope 2.5) in a series of 10 renal cell carcinomas with TFEB gene alterations, either amplification and/or rearrangement (t(6;11) renal cell carcinoma). Outcomes suggest occurrence of VEGFA amplification/increased gene copy number and VEGFA mRNA expression in TFEB-amplified renal cell carcinoma, and also in a subset of t(6;11) renal cell carcinoma displaying aggressive behavior, and in unamplified conventional t(6;11) renal cell carcinoma. This suggests that in these neoplasms, VEGFA could be a potential therapeutic target, even in the absence of TFEB amplification. They recommend performing immunohistochemical examination of all the renal tumors showing morphological characteristics suggesting t(6;11) renal cell carcinoma and all unclassified renal cell carcinomas, either high grade or low grade, for cathepsin K and/or Melan-A; if one of them is positive, they should then investigate for the TFEB gene alteration and VEGFA gene amplification.