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. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1646-E1652, 2016.

Purpose: To determine whether MRI/ultrasound (MRI/US) fusion biopsy facilitates longitudinal resampling of the same clonal focus of prostate cancer and to determine whether high-grade cancers can evolve from low-grade clones.Experimental Design: All men on active surveillance who underwent tracking MRI/US fusion biopsy of Gleason 6 prostate cancer, on at least two distinct occasions, between 2012 and 2014 were enrolled. MRI/US fusion was used to track and resample specific cancer foci. IHC for ERG and targeted RNA/DNA next-generation sequencing (NGS) were performed on formalin-fixed paraffin-embedded prostate biopsy specimens to assess clonality.Results: Thirty-one men with median age and PSA of 65 years and 4.6 ng/mL, respectively, were analyzed. The median sampling interval was 12 months (range, 5-35). Of the 26 evaluable men, ERG IHC concordance was found between initial and repeat biopsies in 25 (96%), indicating resampling of the same clonal focus over time. Targeted NGS supported ERG IHC results and identified unique and shared driving mutations, such as IDH1 and SPOP, in paired specimens. Of the nine men (34.6%) who were found to have Gleason ≥7 on repeat biopsy, all displayed temporal ERG concordance. Prioritized genetic alterations were detected in 50% (13/26) of paired samples. Oncogenic mutations were detected in 22% (2/9) of Gleason 6 cancers prior to progression and 44% (4/9) of Gleason ≥7 cancers when progression occurred.Conclusions: Precise tracking of prostate cancer foci via MRI/US fusion biopsy allowed subsequent resampling of the same clonal focus of cancer over time. Further research is needed to clarify the grade progression potential of Gleason 6 prostate cancer. Clin Cancer Res; 23(4); 985-91. ©2016 AACR.