Prognostic Significance of Oxidation Pathway Mutations in Recurrent Laryngeal Squamous Cell Carcinoma

Abstract

Organ preservation protocols are commonly used as first line therapy for advanced laryngeal cancer. Recurrence thereafter is associated with poor survival. The aim of this study is to identify genetic alterations associated with survival among patients with recurrent laryngeal cancer undergoing salvage laryngectomy. Sixty-two patients were sequenced using a targeted panel, of which twenty-two also underwent transcriptome sequencing. Alterations were grouped based on biologic pathways and survival outcomes were assessed using Kaplan-Meier analysis and multivariate cox regression. Select pathways were evaluated against The Cancer Genome Atlas (TCGA) data. Patients with mutations in the Oxidation pathway had significantly worse five-year disease specific survival (1% vs. 76%, p = 0.02), while mutations in the HN-Immunity pathway were associated with improved five-year disease specific survival (100% vs. 62%, p = 0.02). Multivariate analysis showed mutations in the Oxidation pathway remained an independent predictor of disease specific survival (HR 3.2, 95% CI 1.1–9.2, p = 0.03). Transcriptome analysis of recurrent tumors demonstrated that alterations in the Oxidation pathway were associated a positive Ragnum hypoxia signature score, consistent with enhanced pathway activity. Further, TCGA analyses demonstrated the prognostic value of oxidation pathway alterations in previously untreated disease. Alterations in the Oxidation pathway are associated with survival among patients with recurrent laryngeal cancer. These prognostic genetic biomarkers may inform precision medicine protocols and identify putatively targetable pathways to improve survival in this cohort.

Tumor immune microenvironment alterations using induction cetuximab in a phase II trial of deintensified therapy for p16‐positive oropharynx cancer

“…A summary of sequencing quality statistics including total unique mapped reads for each sample is provided in Table S1, Supporting Information. FPKM and TPM were quantified from the data as previously described 18,19 …”

SearcHPV: A novel approach to identify and assemble human papillomavirus–host genomic integration events in cancer

“…The patient donating TumorA was consented for next‐generation sequencing under a previously described protocol approved by the University of Michigan institutional review board 20 . Targeted capture was performed with a custom‐designed probe panel with high‐density coverage of the HPV‐16 genome, the HPV‐18/33/35 L2/L1 regions, and more than 200 HNSCC‐related genes, which have been detailed by Heft Neal et al 21 After library preparation and capture, the samples were sequenced on an Illumina NovaSEQ6000 or HiSEQ4000, respectively, with a 300‐nt paired‐end run. Data were demultiplexed, and FastQ files were generated.…”

Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma

“…Using the DNA Thruplex kit for library preparation (Takara Biosciences), targeted capture sequencing on DNA that passed our quality control standards was performed by the University of Michigan Advanced Genomics Core as previously described [22]. We employed a custom-designed probe panel from Nextera that included high density probes covering the HPV16 genome as well as probes for targeting several common cancer-related genes [23]. Following library preparation and capture, the samples were sequenced on an Illumina NOVASeq6000 using a 300-cycle run and FastQ files were archived.…”