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<p>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 <i>FGFR</i>, <i>NTRK</i>, and <i>ALK</i> 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 <i>FGFR3</i> fusions (<i>n</i> = 19) and gain-of-function <i>EGFR</i> fusions (<i>n</i> = 6). Fusion-positive HNC had significantly higher gene expression and higher prevalence of human papillomavirus than fusion-negative HNC (<i>p</i> &lt; 0.001). Tumors with <i>FGFR</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月3日

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  • 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

摘要

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.