Abstract 6843: Comprehensive multi-omics approaches for identification of genetic alterations in head and neck squamous cell carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most difficult and challenging malignancies, with a high level of heterogeneity and a wide range of treatment responses, regardless of the clinical stage. Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and accounts for over 90% of cancers that develop in the mucosal epithelium of the oral cavity. Additional carcinogenic risk factors, including tobacco, alcohol, and HPV infection are also associated with the pathogenesis of oral carcinogenesis. Unfortunately, today the failure of standard treatment modalities such as surgery, radiotherapy, and chemotherapy underscore the need for comprehensive genomic profiling to provide a better picture of the genetic alterations and gain an improved understanding of the complex signaling networks involved in the development of potential treatment resistance as well as the identification of novel biomarkers that discriminate between smokers and non-smokers. Methods: A retrospective analysis was performed on biopsied Formalin-Fixed Paraffin-Embedded (FFPE) samples from OSCC patients with and without a history of smoking and treated +/- chemotherapy. Patient samples representing matched normal tissue to serve as controls were compared to tumor squamous cell carcinoma samples and profiled using a single assay panel that includes 517 genes by both DNA and RNA NGS, microsatellite instability (MSI), and tumor mutational burden (TMB). Further analysis was also performed using the NanoString nCounter® PanCancer Immune Profiling Panel (PCIP), 770-comprehensive gene expression panel Results: The Neo ComprehensiveTM Solid Tumor pan cancer assay enabled simultaneously analysis of both DNA and RNA in one integrated workflow with an accompanying DragenTM bioinformatics analysis platform and provided comprehensive genomic profiling of sequence and structural variants, as well as genomic signatures such as TMB and MSI in OSCC patients. Utility of the NanoString PCIP highlighted immune-relevant gene expression changes within the different sample cohorts. The detailed molecular information highlighted by our study emphasizes the need for improved patient classification based on smoking status in the management of OSCC and also in establishing potential therapeutic options based on the many altered cell signaling pathways that we identified. By combining a multi-omics approach with expression data for immune-related genes and associated overall survival data, we provide an effective strategy and workflow for the identification of prognostic biomarkers in OSCC. Citation Format: Kirsteen Maclean, Qinqin Zha, Lakshmi Chandramohan, Anna Juncker-Jensen. Comprehensive multi-omics approaches for identification of genetic alterations in head and neck squamous cell carcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6843.