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Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low-risk patient as defined by targeted sequencing

2016-02-05 00:30:04

Head & Neck; 5 February 2016: DOI:10.1002/hed.24292

Brittny N. Tillman, Megan Yanik, Andrew C. Birkeland, Chia-Jen Liu, Daniel H. Hovelson, Andi K. Cani, Nallasivam Palanisamy PhD, Shannon Carskadon, Thomas E. Carey PhD, Carol R. Bradford MD, Scott A. Tomlins MD, PhD, Jonathan B. McHugh MD, Matthew E. Spector MD, and J. Chad Brenner PhD



Abstract


Background


Targeted sequencing of patients with epidemiologically low-risk (ELR) head and neck squamous cell carcinoma (HNSCC) could help identify novel drivers or lost suppressors leading to precision medicine protocols and improved survival rates.



Methods


A patient with ELR-HNSCC was selected for targeted sequencing. We then assessed next generation sequencing cohorts from the Oncomine Powertool Database, which contains pan-cancer data from The Cancer Genome Atlas (TCGA).



Results


Targeted sequencing revealed fibroblast growth factor receptor-1 (FGFR1) amplifications as a putative driver of the patient's tumor. Patients with HNSCC from TCGA data demonstrated fibroblast growth factor (FGF) family mutations, rearrangements, or amplifications in over 35% of HNSCC cases, with a statistically significant higher frequency in African American populations. FGF alterations were unique from activating phosphatidylinositol 3-kinase (PIK3CA) mutations.



Conclusion


Together, these data suggest that FGF signaling may be critical for a subset of patients with HNSCC independent of other known pathways and provides rationale for leveraging patients with ELR-HNSCC to define molecular subsets of high-risk HNSCC.



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Key Words


head and neck squamous cell carcinoma (HNSCC) | fibroblast growth factor (FGF) | fibroblast growth factor receptor (FGFR) | amplification | mutant