AUTHOR=Yu Qing-Xiang , Zhao Wen-Jun , Wang He-Yue , Zhang Lei , Qin Lan , Zhang Lei , Han Jian-li 

TITLE=Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1123812

DOI=10.3389/fonc.2023.1123812

ISSN=2234-943X

ABSTRACT=<p><italic>NTRK</italic> fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in <italic>NTRK</italic>-positive solid tumors. Although some <italic>NTRK</italic> fusion partners have been identified in thyroid cancer, the spectrum of <italic>NTRK</italic> fusion is not fully characterized. In this study, a dual <italic>NTRK3</italic> fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between <italic>NTRK3</italic> exon 13 and <italic>AJUBA</italic> exon 2, co-existing with a known in-frame fusion between <italic>ETV6</italic> exon 4 and <italic>NTRK3</italic> exon 14. The dual <italic>NTRK3</italic> fusion was validated by Sanger sequencing and fluorescence <italic>in situ</italic> hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel <italic>NTRK3-AJUBA</italic> fusion co-existing with a known <italic>ETV6-NTRK3</italic> fusion in thyroid cancer. These findings extend the spectrum of translocation partners in <italic>NTRK3</italic> fusion, and the effect of dual <italic>NTRK3</italic> fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.</p>