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

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

doi:10.1038/s41698-025-00889-7

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

NPJ Precis Oncol. 2025 Jul 3;9(1):221. doi: 10.1038/s41698-025-00889-7.

Authors

Emily L Hoskins^{1

2}, Raven Vella^{1

2

3}, Julie W Reeser¹, Michele R Wing¹, Eric Samorodnitsky¹, Altan Turkoglu^{1

2

3}, Leah Stein^{1

2}, Elizabeth Breuning⁴, Zachary A Risch¹, Wilnelly M Hernandez-Sanchez⁵, Lianbo Yu⁶, Michelle Churchman⁷, Nancy Single¹, Jad Chahoud⁸, Antonio Jimeno⁹, Michael J Cavnar¹⁰, Matthew Reilley¹¹, Courtney Scaife¹², Kenneth G Nepple¹³, Minh Phan¹⁴, Bryan Schneider¹⁵, Stephen Edge¹⁶, Bodour Salhia¹⁷, Aliza Leiser¹⁸, Trisha M Wise-Draper¹⁹, Michael K Wendt²⁰, Sameek Roychowdhury²¹

Affiliations

¹ Comprehensive Cancer Center and James Cancer Hospital, The Ohio State University, Columbus, OH, USA.
² Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA.
³ Medical Sciences Training Program, The Ohio State University, Columbus, OH, USA.
⁴ The Bioinformatics Program, Loyola University Chicago, Chicago, IL, USA.
⁵ Caris Life Sciences, Irving, TX, USA.
⁶ Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
⁷ Aster Insights, Tampa, FL, USA.
⁸ Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁹ Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA.
¹⁰ Division of Surgical Oncology, Department of Surgery, University of Kentucky Markey Comprehensive Cancer Center, Lexington, KY, USA.
¹¹ Division of Hematology and Oncology, Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA.
¹² Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹³ Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
¹⁴ Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Ok, USA.
¹⁵ Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁶ Roswell Park Cancer Institute, University at Buffalo, Buffalo, NY, USA.
¹⁷ Department of Neurosurgery Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁸ Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
¹⁹ Division of Hematology and Oncology, University of Cincinnati, Cincinnati, OH, USA.
²⁰ Division of Hematology and Oncology, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
²¹ Comprehensive Cancer Center and James Cancer Hospital, The Ohio State University, Columbus, OH, USA. Sameek.roychowdhury@osumc.edu.

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.

Abstract

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