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 (<i>KIF5B</i>)-<i>NTRK1</i> gene fusion that responds well to entrectinib. Moreover, <i>KIF5B</i>-<i>NTRK1</i> gene chimera has been shown to be an oncogene,...
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2024-10-01
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| Series: | Current Oncology |
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| author | Hui Li Huicong Liu Lisha Xiao Huabin Gao Huiting Wei Anjia Han Gengpeng Lin |
| author_facet | Hui Li Huicong Liu Lisha Xiao Huabin Gao Huiting Wei Anjia Han Gengpeng Lin |
| author_sort | Hui Li |
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| description | We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (<i>KIF5B</i>)-<i>NTRK1</i> gene fusion that responds well to entrectinib. Moreover, <i>KIF5B</i>-<i>NTRK1</i> 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 <i>KIF5B</i>-<i>NTRK1</i> 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 <i>KIF5B</i>-<i>NTRK1</i> 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 <i>NTRK</i> gene fusions in the context of lung adenocarcinoma. |
| format | Article |
| id | doaj-art-cb8bb68df74c46bb9c120cdf1935b3ed |
| institution | OA Journals |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj-art-cb8bb68df74c46bb9c120cdf1935b3ed2025-08-20T02:07:59ZengMDPI AGCurrent Oncology1198-00521718-77292024-10-0131116621663110.3390/curroncol31110489A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung AdenocarcinomaHui Li0Huicong Liu1Lisha Xiao2Huabin Gao3Huiting Wei4Anjia Han5Gengpeng Lin6Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou 510080, ChinaWe present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (<i>KIF5B</i>)-<i>NTRK1</i> gene fusion that responds well to entrectinib. Moreover, <i>KIF5B</i>-<i>NTRK1</i> 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 <i>KIF5B</i>-<i>NTRK1</i> 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 <i>KIF5B</i>-<i>NTRK1</i> 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 <i>NTRK</i> gene fusions in the context of lung adenocarcinoma.https://www.mdpi.com/1718-7729/31/11/489KIF5B-NTRK1lung adenocarcinomaentrectinibsignaling pathwayscase report |
| spellingShingle | Hui Li Huicong Liu Lisha Xiao Huabin Gao Huiting Wei Anjia Han Gengpeng Lin A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma Current Oncology KIF5B-NTRK1 lung adenocarcinoma entrectinib signaling pathways case report |
| title | A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma |
| title_full | A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma |
| title_fullStr | A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma |
| title_full_unstemmed | A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma |
| title_short | A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma |
| title_sort | novel oncogenic and drug sensitive kif5b ntrk1 fusion in lung adenocarcinoma |
| topic | KIF5B-NTRK1 lung adenocarcinoma entrectinib signaling pathways case report |
| url | https://www.mdpi.com/1718-7729/31/11/489 |
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