Scheiter, Alexander and Keil, Felix and Lueke, Florian and Grosse, Jirka and Verloh, Niklas and Opitz, Sabine and Schlosser, Sophie and Kandulski, Arne and Pukrop, Tobias and Dietmaier, Wolfgang and Evert, Matthias and Calvisi, Diego F. and Utpatel, Kirsten (2021) Identification and In-Depth Analysis of the Novel FGFR2-NDC80 Fusion in a Cholangiocarcinoma Patient: Implication for Therapy. CURRENT ONCOLOGY, 28 (2). pp. 1161-1169. ISSN 1198-0052, 1718-7729
Full text not available from this repository. (Request a copy)Abstract
Fibroblast growth factor receptor 2 (FGFR2) fusions have emerged as a new therapeutic target for cholangiocarcinoma in clinical practice following the United States Food and Drug Administration (FDA) approval of Pemigatinib in May 2020. FGFR2 fusions can result in a ligand-independent constitutive activation of FGFR2 signaling with a downstream activation of multiple pathways, including the mitogen-activated protein (MAPK) cascade. Until today, only a limited number of fusion partners have been reported, of which the most prevalent is BicC Family RNA Binding Protein (BICC1), representing one-third of all detected FGFR2 fusions. Nonetheless, in the majority of cases rare or yet unreported fusion partners are discovered in next-generation sequencing panels, which confronts clinicians with a challenging decision: Should a therapy be based on these variants or should the course of treatment follow the (limited) standard regime? Here, we present the case of a metastasized intrahepatic cholangiocarcinoma harboring a novel FGFR2-NDC80 fusion, which was discussed in our molecular tumor board. The protein NDC80 kinetochore complex component (NDC80) is an integral part of the outer kinetochore, which is involved in microtubule binding and spindle assembly. For additional therapeutic guidance, an immunohistochemical analysis of the predicted fusion and downstream effector proteins was performed and compared to cholangiocarcinoma samples of a tissue microarray. The FGFR2-NDC80 fusion resulted in strong activation of the FGFR2 signaling pathway. These supporting results led to a treatment recommendation of Pemigatinib. Unfortunately, the patient passed away before the commencement of therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MULTICENTER; CANCER; FGFR; cholangiocarcinoma; FGFR fusion; NDC80; FRS2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie Medicine > Lehrstuhl für Röntgendiagnostik Medicine > Abteilung für Nuklearmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jul 2022 08:46 |
| Last Modified: | 06 Jul 2022 08:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45664 |
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