Identification of a Novel EHBP1 - MET Fusion in an Intrahepatic Cholangiocarcinoma Responding to Crizotinib

Abstract

As an aggressive tumor, intrahepatic cholangiocarcinoma (ICC) originates in the epithelium of the bile duct and has a poor prognosis. The therapeutic options for ICC are challenging and limited due to poor response to chemotherapy and the lack of targeted therapy. Here we report a 41-year-old female ICC patient with EHBP1-MET fusion and multiple intrahepatic metastases responding to crizotinib. Next-generation sequencing (NGS) based tumor mutation profiling was performed on the tumor biopsy and ctDNA from plasma. A novel EHBP1-MET fusion was identified and confirmed by Sanger sequencing. Immunohistochemistry (IHC) of biopsy sample also revealed positive for c-MET. Subsequently, the patient started treatment with MET inhibitors crizotinib. Magnetic resonance imaging (MRI) scan demonstrated a partial response for 8 months. To the best of our knowledge, this is the first clinical case report of a MET rearranged-ICC patient successfully treated with crizotinib. This case suggests that crizotinib may be a promising treatment option for ICC patients with MET fusion, warranting further clinical investigation. KEY POINTS: To our knowledge, this is the first reported case of EHBP1-MET fusion. This is also the first clinical case report of clinical benefit from crizotinib treatment in an ICC with MET fusion. MET fusion is rare in ICC, and inhibition of MET could be a viable option for ICC which warrants further clinical investigation.