<i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer
<b>Background/Objectives:</b> Since the discovery of oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusions in colorectal cancer in 1986, their understanding has evolved, particularly in non-small-cell lung cancer (NSCLC) over the past five years. NTRK rearrangements, involv...
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2025-02-01
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| author | Jair Gutierrez-Herrera M. Angeles Montero-Fernandez Georgia Kokaraki Luigi De Petris Raul Maia Falcão Manuel Molina-Centelles Ricardo Guijarro Simon Ekman Cristian Ortiz-Villalón |
| author_facet | Jair Gutierrez-Herrera M. Angeles Montero-Fernandez Georgia Kokaraki Luigi De Petris Raul Maia Falcão Manuel Molina-Centelles Ricardo Guijarro Simon Ekman Cristian Ortiz-Villalón |
| author_sort | Jair Gutierrez-Herrera |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Since the discovery of oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusions in colorectal cancer in 1986, their understanding has evolved, particularly in non-small-cell lung cancer (NSCLC) over the past five years. NTRK rearrangements, involving NTRK1, NTRK2, and NTRK3, drive tumorigenesis and have been identified in various adult and pediatric cancers, with over 80 different fusion variants in several type of cancers. Detecting these rearrangements is crucial for targeted therapy strategies. The aim of this study is detect, compare and analyse these mutations in NSCLC patients of a cohort of 482 cases from Karolinska University Hospital. <b>Methods:</b> We conducted an initial screening using pan-TRK immunohistochemistry (IHC) to analyze the material. Positive cases were further examined through whole-exome sequencing (WES) with next-generation sequencing (NGS) to confirm the presence of fusions. Additionally, to deepen our understanding, we utilized Ingenuity Pathway Analysis (IPA) software, an artificial intelligence-driven technology, to explore the molecular pathways involved in lung cancer. <b>Results:</b> TRK overexpression was detected in 4.56% of cases via IHC. Among 15 pan-TRK-positive cases, WES confirmed fusions in 3, revealing a higher prevalence of NTRK1 (6.6%) and NTRK2 (13.3%) fusions, while no NTRK3 fusions were observed. <b>Conclusions:</b> Our findings confirm the low prevalence of these neoplasms as well as the need for a molecular test to confirm rearrangements or other potentially treatable mutations and raise other questions regarding their clinical use. However, there is an acceptable correlation between pan-TRK IHC and NTRK mutations, but not enough to determine NTRK fusions. |
| format | Article |
| id | doaj-art-06dedd344a5347758785aa4f53889563 |
| institution | DOAJ |
| issn | 2673-527X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Journal of Respiration |
| spelling | doaj-art-06dedd344a5347758785aa4f538895632025-08-20T02:42:32ZengMDPI AGJournal of Respiration2673-527X2025-02-0151210.3390/jor5010002<i>NTRK</i> Gene Expression in Non-Small-Cell Lung CancerJair Gutierrez-Herrera0M. Angeles Montero-Fernandez1Georgia Kokaraki2Luigi De Petris3Raul Maia Falcão4Manuel Molina-Centelles5Ricardo Guijarro6Simon Ekman7Cristian Ortiz-Villalón8Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 182 88 Stockholm, SwedenDepartment of Cellular Pathology, Liverpool University NHS Foundation Trust, Liverpool L7 8XP, UKDepartment of Oncology-Pathology (Onkpat), Karolinska Institute, 171 64 Stockholm, SwedenDepartment of Oncology-Pathology (Onkpat), Karolinska Institute, 171 64 Stockholm, SwedenMetrópole Digital Institute, Federal University of Rio Grande do Norte, Natal 59066-800, BrazilDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, 182 88 Stockholm, SwedenDepartment of Oncology-Pathology (Onkpat), Karolinska Institute, 171 64 Stockholm, SwedenDepartment of Oncology-Pathology (Onkpat), Karolinska Institute, 171 64 Stockholm, SwedenDepartment of Oncology-Pathology (Onkpat), Karolinska Institute, 171 64 Stockholm, Sweden<b>Background/Objectives:</b> Since the discovery of oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusions in colorectal cancer in 1986, their understanding has evolved, particularly in non-small-cell lung cancer (NSCLC) over the past five years. NTRK rearrangements, involving NTRK1, NTRK2, and NTRK3, drive tumorigenesis and have been identified in various adult and pediatric cancers, with over 80 different fusion variants in several type of cancers. Detecting these rearrangements is crucial for targeted therapy strategies. The aim of this study is detect, compare and analyse these mutations in NSCLC patients of a cohort of 482 cases from Karolinska University Hospital. <b>Methods:</b> We conducted an initial screening using pan-TRK immunohistochemistry (IHC) to analyze the material. Positive cases were further examined through whole-exome sequencing (WES) with next-generation sequencing (NGS) to confirm the presence of fusions. Additionally, to deepen our understanding, we utilized Ingenuity Pathway Analysis (IPA) software, an artificial intelligence-driven technology, to explore the molecular pathways involved in lung cancer. <b>Results:</b> TRK overexpression was detected in 4.56% of cases via IHC. Among 15 pan-TRK-positive cases, WES confirmed fusions in 3, revealing a higher prevalence of NTRK1 (6.6%) and NTRK2 (13.3%) fusions, while no NTRK3 fusions were observed. <b>Conclusions:</b> Our findings confirm the low prevalence of these neoplasms as well as the need for a molecular test to confirm rearrangements or other potentially treatable mutations and raise other questions regarding their clinical use. However, there is an acceptable correlation between pan-TRK IHC and NTRK mutations, but not enough to determine NTRK fusions.https://www.mdpi.com/2673-527X/5/1/2predictive biomarkers in non-small-cell lung cancerNTRK status in tumor cellswhole exome sequencingWES–NGSingenuity pathway analysis (IPA) |
| spellingShingle | Jair Gutierrez-Herrera M. Angeles Montero-Fernandez Georgia Kokaraki Luigi De Petris Raul Maia Falcão Manuel Molina-Centelles Ricardo Guijarro Simon Ekman Cristian Ortiz-Villalón <i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer Journal of Respiration predictive biomarkers in non-small-cell lung cancer NTRK status in tumor cells whole exome sequencing WES–NGS ingenuity pathway analysis (IPA) |
| title | <i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer |
| title_full | <i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer |
| title_fullStr | <i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer |
| title_full_unstemmed | <i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer |
| title_short | <i>NTRK</i> Gene Expression in Non-Small-Cell Lung Cancer |
| title_sort | i ntrk i gene expression in non small cell lung cancer |
| topic | predictive biomarkers in non-small-cell lung cancer NTRK status in tumor cells whole exome sequencing WES–NGS ingenuity pathway analysis (IPA) |
| url | https://www.mdpi.com/2673-527X/5/1/2 |
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