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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00889-7
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Summary: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.
ISSN:2397-768X