AUTHOR=Chen Yanming , Zhu Qing , Wang Ye , Dai Xiaoxiao , Chen Ping , Chen Ailin , Zhou Sujuan , Dai Chungang , Zhao Shengbin , Xiao Sheng , Lan Qing 

TITLE=Case Report: A novel LHFPL3::NTRK2 fusion in dysembryoplastic neuroepithelial tumor

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1064817

DOI=10.3389/fonc.2022.1064817

ISSN=2234-943X

ABSTRACT=<p>Neurotrophic tyrosine receptor kinase (<italic>NTRK</italic>) rearrangements are oncogenic drivers of various types of adult and pediatric tumors, including gliomas. However, <italic>NTRK</italic> rearrangements are extremely rare in glioneuronal tumors. Here, we report a novel <italic>NTRK2</italic> rearrangement in a 24-year-old female with dysembryoplastic neuroepithelial tumor (DNT), a circumscribed WHO grade I benign tumor associated with epilepsy. By utilizing targeted RNA next-generation sequencing (NGS), fluorescence <italic>in situ</italic> hybridization (FISH), reverse transcriptase PCR (RT-PCR), and Sanger sequencing, we verified an in-frame fusion between <italic>NTRK2</italic> and the lipoma <italic>HMGIC</italic> fusion partner-like 3 (<italic>LHFPL3</italic>). This oncogenic gene rearrangement involves 5’ <italic>LHFPL3</italic> and 3’ <italic>NTRK2</italic>, retaining the entire tyrosine kinase domain of <italic>NTRK2</italic> genes. Moreover, the targeted DNA NGS analysis revealed an <italic>IDH1</italic> (p.R132H) mutation, a surprising finding in this type of tumor. The pathogenic mechanism of the <italic>LHFPL3::NTRK2</italic> in this case likely involves aberrant dimerization and constitutive activation of RTK signaling pathways.</p>