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

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

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English
Article number	221
Journal	npj Precision Oncology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41698-025-00889-7
State	Published - Dec 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

We would like to thank the Ohio Supercomputer Center (https://www.osc.edu/) for providing the Owens cluster on which this work was performed. We would like to thank Barb Hughes and Jenny Badillo for their administrative assistance.

Funders
Ohio Supercomputer Center

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/s41698-025-00889-7

Cite this

Hoskins, E. L., Vella, R., Reeser, J. W., Wing, M. R., Samorodnitsky, E., Turkoglu, A., Stein, L., Breuning, E., Risch, Z. A., Hernandez-Sanchez, W. M., Yu, L., Churchman, M., Single, N., Chahoud, J., Jimeno, A., Cavnar, M. J., Reilley, M., Scaife, C., Nepple, K. G., ... Roychowdhury, S. (2025). Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers. npj Precision Oncology, 9(1), Article 221. https://doi.org/10.1038/s41698-025-00889-7

@article{74afdd8bfb6f4ccca0dc492b1ae2283e,

title = "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, 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.",

author = "Hoskins, \{Emily L.\} and Raven Vella and Reeser, \{Julie W.\} and Wing, \{Michele R.\} and Eric Samorodnitsky and Altan Turkoglu and Leah Stein and Elizabeth Breuning and Risch, \{Zachary A.\} and Hernandez-Sanchez, \{Wilnelly M.\} and Lianbo Yu and Michelle Churchman and Nancy Single and Jad Chahoud and Antonio Jimeno and Cavnar, \{Michael J.\} and Matthew Reilley and Courtney Scaife and Nepple, \{Kenneth G.\} and Minh Phan and Bryan Schneider and Stephen Edge and Bodour Salhia and Aliza Leiser and Wise-Draper, \{Trisha M.\} and Wendt, \{Michael K.\} and Sameek Roychowdhury",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41698-025-00889-7",

language = "English",

volume = "9",

number = "1",

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Hoskins, EL, Vella, R, Reeser, JW, Wing, MR, Samorodnitsky, E, Turkoglu, A, Stein, L, Breuning, E, Risch, ZA, Hernandez-Sanchez, WM, Yu, L, Churchman, M, Single, N, Chahoud, J, Jimeno, A, Cavnar, MJ, Reilley, M, Scaife, C, Nepple, KG, Phan, M, Schneider, B, Edge, S, Salhia, B, Leiser, A, Wise-Draper, TM, Wendt, MK & Roychowdhury, S 2025, 'Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers', npj Precision Oncology, vol. 9, no. 1, 221. https://doi.org/10.1038/s41698-025-00889-7

TY - JOUR

T1 - Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers

AU - Hoskins, Emily L.

AU - Vella, Raven

AU - Reeser, Julie W.

AU - Wing, Michele R.

AU - Samorodnitsky, Eric

AU - Turkoglu, Altan

AU - Stein, Leah

AU - Breuning, Elizabeth

AU - Risch, Zachary A.

AU - Hernandez-Sanchez, Wilnelly M.

AU - Yu, Lianbo

AU - Churchman, Michelle

AU - Single, Nancy

AU - Chahoud, Jad

AU - Jimeno, Antonio

AU - Cavnar, Michael J.

AU - Reilley, Matthew

AU - Scaife, Courtney

AU - Nepple, Kenneth G.

AU - Phan, Minh

AU - Schneider, Bryan

AU - Edge, Stephen

AU - Salhia, Bodour

AU - Leiser, Aliza

AU - Wise-Draper, Trisha M.

AU - Wendt, Michael K.

AU - Roychowdhury, Sameek

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/105014092140#tab=citedBy

U2 - 10.1038/s41698-025-00889-7

DO - 10.1038/s41698-025-00889-7

M3 - Article

AN - SCOPUS:105014092140

VL - 9

JO - npj Precision Oncology

JF - npj Precision Oncology

IS - 1

M1 - 221

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

Access to Document

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Cite this