Abstract B012: A comparative accuracy analysis of local ancestry calling from targeted sequencing panels in head and neck squamous cell carcinoma

Abstract

Targeted gene panels are increasingly used in clinical oncology, but their utility for local ancestry inference remains poorly characterized relative to whole-genome and whole-exome sequencing (WGS/WES). If sufficiently accurate, panel-based ancestry estimation could enable a cost-effective approach for ancestry-informed cancer genomics and precision oncology. Head and neck squamous cell carcinoma (HNSCC) exhibits significant survival disparities by ancestry, with patients of African descent having two times the relative risk of death compared to European patients. Additionally, emerging evidence indicates that genetic ancestry independently shapes HNSCC tumor biology, including gene expression, mutational spectrum, copy number alterations, and DNA methylation. Incorporating ancestry into HNSCC genomic analysis through accurate, low-cost genomic panels will allow for further exploration of these survival disparities. We evaluate the performance of the Tempus targeted panel for local ancestry calling and somatic mutation detection in head and neck squamous cell carcinoma (HNSCC). Using The Cancer Genome Atlas (TCGA) HNSCC cohort (n=440), we compared local ancestry-calling accuracy derived from WES and Tempus gene panel relative to WGS, as the reference standard. Accuracy was assessed genome-wide and at individual genes frequently mutated in HNSCC to determine whether panel-based ancestry calls remain reliable in genomic regions of clinical interest. We also assessed somatic mutation calling performance on the Tempus panel. Local ancestry inference achieved 91% and 90% accuracy for WES and the Tempus panel, respectively, compared to WGS. Accuracy at individual HNSCC driver genes ranges from 71-97% for WES and 74-95% for Tempus. Despite substantially reduced genomic coverage, the Tempus panel demonstrated ancestry-calling performance comparable to WES while retaining the ability to identify clinically relevant somatic variants. Targeted sequencing panels, such as those from Tempus, can provide accurate local ancestry estimates with performance approaching that of WES and WGS, supporting their use for ancestry-informed genomic analysis. These findings highlight the potential of clinically deployed panels such as Tempus to enable scalable and cost-effective integration of ancestry into precision oncology studies. Madeleine Ndahayo, Roland Laboulaye, Jeremy Wilson, Yang Song, Ranee Mehra, Timothy D. O'Connor, Daria A. Gaykalova. A comparative accuracy analysis of local ancestry calling from targeted sequencing panels in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr B012.