Urothelial carcinoma with an rearrangement and response to targeted therapy.

Although mutations are commonly identified in many solid tumors and the response of p.V600E-positive tumors to targeted therapy is well documented, rearrangements are less frequent and are predominantly found in low-grade glioma, melanoma, lung, colorectal, and thyroid carcinoma. Preclinical and clinical studies have demonstrated effectiveness of multiple therapies (RAF-targeted, ERK-targeted, or MEK-targeted) targeting -fusion harboring tumors. We report a rare fusion with novel breakpoints, identified by next-generation sequencing-based assay, from a 69-year-old man with metastatic urothelial carcinoma (UC) of the renal pelvis and his initial clinical response to a second-generation MEK inhibitor, trametinib, before stopping the medication because of adverse side effects. The fusion has only been reported in a single case of anaplastic pleomorphic xanthoastrocytoma, and rearrangement has never been reported in UC.