Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers
Abstract Head and neck cancer (HNC) is the seventh most common cancer worldwide. Currently-approved systemic therapies include chemotherapy, anti-EGFR antibodies, and PD-1 immunotherapy, with few genomic-based targeted therapies. Gene fusions involving cancer-driving kinase genes such as FGFR, NTRK,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00889-7 |
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| author | Emily L. Hoskins Raven Vella Julie W. Reeser Michele R. Wing Eric Samorodnitsky Altan Turkoglu Leah Stein Elizabeth Breuning Zachary A. Risch Wilnelly M. Hernandez-Sanchez Lianbo Yu Michelle Churchman Nancy Single Jad Chahoud Antonio Jimeno Michael J. Cavnar Matthew Reilley Courtney Scaife Kenneth G. Nepple Minh Phan Bryan Schneider Stephen Edge Bodour Salhia Aliza Leiser Trisha M. Wise-Draper Michael K. Wendt Sameek Roychowdhury |
| author_facet | Emily L. Hoskins Raven Vella Julie W. Reeser Michele R. Wing Eric Samorodnitsky Altan Turkoglu Leah Stein Elizabeth Breuning Zachary A. Risch Wilnelly M. Hernandez-Sanchez Lianbo Yu Michelle Churchman Nancy Single Jad Chahoud Antonio Jimeno Michael J. Cavnar Matthew Reilley Courtney Scaife Kenneth G. Nepple Minh Phan Bryan Schneider Stephen Edge Bodour Salhia Aliza Leiser Trisha M. Wise-Draper Michael K. Wendt Sameek Roychowdhury |
| author_sort | Emily L. Hoskins |
| collection | DOAJ |
| description | Abstract Head and neck cancer (HNC) is the seventh most common cancer worldwide. Currently-approved systemic therapies include chemotherapy, anti-EGFR antibodies, and PD-1 immunotherapy, with few genomic-based targeted therapies. Gene fusions involving cancer-driving kinase genes such as FGFR, NTRK, and ALK are clinically targetable in other solid tumors; however, there is limited knowledge about their prevalence in HNC. Here, we describe the genomic landscape and the biological impact of oncogenic fusions in a combined dataset of over 13,000 HNC tumors (excluding salivary gland tumors). We identified 66 cases (2.8%) harboring oncogenic fusions, including previously-reported FGFR3 fusions (n = 19) and gain-of-function EGFR fusions (n = 6). Fusion-positive HNC had significantly higher gene expression and higher prevalence of human papillomavirus than fusion-negative HNC (p < 0.001). Tumors with FGFR alterations were associated with enriched cell proliferation and higher abundance of NK cells and CD8+ T cells compared to wildtype. Our results provide expanded therapeutic opportunities for patients with HNCs. |
| format | Article |
| id | doaj-art-6293061419a64c888d514b4a3b8b8c82 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-6293061419a64c888d514b4a3b8b8c822025-08-20T03:45:18ZengNature Portfolionpj Precision Oncology2397-768X2025-07-019111310.1038/s41698-025-00889-7Prevalence and biological impact of clinically relevant gene fusions in head and neck cancersEmily L. Hoskins0Raven Vella1Julie W. Reeser2Michele R. Wing3Eric Samorodnitsky4Altan Turkoglu5Leah Stein6Elizabeth Breuning7Zachary A. Risch8Wilnelly M. Hernandez-Sanchez9Lianbo Yu10Michelle Churchman11Nancy Single12Jad Chahoud13Antonio Jimeno14Michael J. Cavnar15Matthew Reilley16Courtney Scaife17Kenneth G. Nepple18Minh Phan19Bryan Schneider20Stephen Edge21Bodour Salhia22Aliza Leiser23Trisha M. Wise-Draper24Michael K. Wendt25Sameek Roychowdhury26Comprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityThe Bioinformatics Program, Loyola University ChicagoComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityCaris Life SciencesDepartment of Biomedical Informatics, The Ohio State UniversityAster InsightsComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityDepartment of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research InstituteDepartment of Surgery, University of Colorado School of MedicineDivision of Surgical Oncology, Department of Surgery, University of Kentucky Markey Comprehensive Cancer CenterDivision of Hematology and Oncology, Department of Medicine, University of Virginia Health SystemDepartment of Surgery, University of Utah School of MedicineDepartment of Urology, University of Iowa Hospitals and ClinicsDepartment of Medicine, University of Oklahoma Health Sciences CenterIndiana University School of MedicineRoswell Park Cancer Institute, University at BuffaloDepartment of Neurosurgery Surgery, Keck School of Medicine, University of Southern CaliforniaRutgers Cancer Institute of New JerseyDivision of Hematology and Oncology, University of CincinnatiDivision of Hematology and Oncology, Department of Internal Medicine, University of IowaComprehensive Cancer Center and James Cancer Hospital, The Ohio State UniversityAbstract Head and neck cancer (HNC) is the seventh most common cancer worldwide. Currently-approved systemic therapies include chemotherapy, anti-EGFR antibodies, and PD-1 immunotherapy, with few genomic-based targeted therapies. Gene fusions involving cancer-driving kinase genes such as FGFR, NTRK, and ALK are clinically targetable in other solid tumors; however, there is limited knowledge about their prevalence in HNC. Here, we describe the genomic landscape and the biological impact of oncogenic fusions in a combined dataset of over 13,000 HNC tumors (excluding salivary gland tumors). We identified 66 cases (2.8%) harboring oncogenic fusions, including previously-reported FGFR3 fusions (n = 19) and gain-of-function EGFR fusions (n = 6). Fusion-positive HNC had significantly higher gene expression and higher prevalence of human papillomavirus than fusion-negative HNC (p < 0.001). Tumors with FGFR alterations were associated with enriched cell proliferation and higher abundance of NK cells and CD8+ T cells compared to wildtype. Our results provide expanded therapeutic opportunities for patients with HNCs.https://doi.org/10.1038/s41698-025-00889-7 |
| spellingShingle | Emily L. Hoskins Raven Vella Julie W. Reeser Michele R. Wing Eric Samorodnitsky Altan Turkoglu Leah Stein Elizabeth Breuning Zachary A. Risch Wilnelly M. Hernandez-Sanchez Lianbo Yu Michelle Churchman Nancy Single Jad Chahoud Antonio Jimeno Michael J. Cavnar Matthew Reilley Courtney Scaife Kenneth G. Nepple Minh Phan Bryan Schneider Stephen Edge Bodour Salhia Aliza Leiser Trisha M. Wise-Draper Michael K. Wendt Sameek Roychowdhury Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers npj Precision Oncology |
| title | Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers |
| title_full | Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers |
| title_fullStr | Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers |
| title_full_unstemmed | Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers |
| title_short | Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers |
| title_sort | prevalence and biological impact of clinically relevant gene fusions in head and neck cancers |
| url | https://doi.org/10.1038/s41698-025-00889-7 |
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