Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers

Authors

• Emily L. Hoskins, Ohio State University
• Raven Vella, Ohio State University
• Julie W. Reeser, Ohio State University
• Michele R. Wing, Ohio State University
• Eric Samorodnitsky, Ohio State University
• Altan Turkoglu, Ohio State University
• Leah Stein, Ohio State University
• Elizabeth Breuning, Loyola University of Chicago
• Zachary A. Risch, Ohio State University
• Wilnelly M. Hernandez-Sanchez, Caris Life Sciences
• Lianbo Yu, Ohio State University
• Michelle Churchman, Aster Insights
• Nancy Single, Ohio State University
• Jad Chahoud, University of South Florida
• Antonio Jimeno, University of Colorado Hospital Denver
• Michael J. Cavnar, University of KentuckyFollow
• Matthew Reilley, University of Virginia
• Courtney Scaife, University of Utah
• Kenneth G. Nepple, University of Iowa Hospitals and Clinics
• Minh Phan, University of Oklahoma
• Bryan Schneider, Indiana University School of Medicine
• Stephen Edge, SUNY Buffalo
• Bodour Salhia, University of Southern California
• Aliza Leiser, Rutgers - The State University of New Jersey, New Brunswick
• Trisha M. Wise-Draper, University of Cincinnati
• Michael K. Wendt, University of Iowa Carver College of Medicine
• Sameek Roychowdhury, Ohio State UniversityFollow

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.

Document Type

Article

Publication Date

12-1-2025

Notes/Citation Information

Publisher Copyright: © The Author(s) 2025.

Digital Object Identifier (DOI)

10.1038/s41698-025-00889-7

Archival?

Archival

Repository Citation

Hoskins, Emily L.; Vella, Raven; Reeser, Julie W.; Wing, Michele R.; Samorodnitsky, Eric; Turkoglu, Altan; Stein, Leah; Breuning, Elizabeth; Risch, Zachary A.; Hernandez-Sanchez, Wilnelly M.; Yu, Lianbo; Churchman, Michelle; Single, Nancy; Chahoud, Jad; Jimeno, Antonio; Cavnar, Michael J.; Reilley, Matthew; Scaife, Courtney; Nepple, Kenneth G.; Phan, Minh; Schneider, Bryan; Edge, Stephen; Salhia, Bodour; Leiser, Aliza; Wise-Draper, Trisha M.; Wendt, Michael K.; and Roychowdhury, Sameek, "Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers" (2025). Surgery Faculty Publications. 69.
https://uknowledge.uky.edu/surgery_facpub/69