A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma.
We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (KIF5B)-NTRK1 gene fusion that responds well to entrectinib. Moreover, KIF5B-NTRK1 gene chimera has been shown to be an oncogene, activating both the MAPK and PI3K/AKT signaling pathways. The biopsy sample...
| Publicado en: | Current Oncology Vol. 31; no. 11; pp. 6621 - 6632 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
MDPI
Nov2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=181170850&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 181170850 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11980052 5EKK jtl: Current Oncology issn: 11980052 maglogo: N pubinfo: dt: Nov2024 vid: 31 iid: 11 pid: 97109 pub: MDPI artinfo: ui: 181170850 10.3390/curroncol31110489 181170850 ppf: 6621 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma. aug: au: Li, Hui Liu, Huicong Xiao, Lisha Gao, Huabin Wei, Huiting Han, Anjia Lin, Gengpeng affil: Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China sug: ab: We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (KIF5B)-NTRK1 gene fusion that responds well to entrectinib. Moreover, KIF5B-NTRK1 gene chimera has been shown to be an oncogene, activating both the MAPK and PI3K/AKT signaling pathways. The biopsy sample was analyzed using various methods such as hematoxylin–eosin staining (HE), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) based on a 1267-gene panel. Additionally, human lung adenocarcinoma cell lines A549 and H1755 were used to obtain a stable expression of chimera gene products. The cell proliferation was confirmed using CCK8 and adhesion-dependent colony formation assay. Cell invasion was confirmed using the transwell invasion assay. The protein levels of the MAPK and PI3K/AKT signaling pathways were assessed using Western blotting. The patient, a 66-year-old Chinese male, was diagnosed with adenocarcinoma (stage IVB) located in the upper lobe of the left lung. NGS analysis identified a novel KIF5B-NTRK1 fusion gene, which was further confirmed by FISH and IHC analyses. As a first-line therapy, entrectinib was administered to the patient at a dose of 600 mg once daily, resulting in a partial response. The patient's progression-free survival (PFS) has now been more than 12 months, and no serious toxicities have been observed so far. Furthermore, stable KIF5B-NTRK1-expressing cells were generated and the experimental results demonstrate enhanced proliferation abilities, along with increased levels of proteins involved in the MAPK and PI3K/AKT signaling pathways. Our study reports a novel KIF5B-NTRK1 genetic rearrangement that supports favorable responses to entrectinib. Moreover, in vitro experiments showed that the fusion gene could exert oncogenic properties by activating the MAPK and PI3K/AKT signaling pathways. To summarize, our findings broaden the spectrum of NTRK gene fusions in the context of lung adenocarcinoma. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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