Abstract 1765: The genetic landscape of head and neck cancer using brush biopsy

Abstract Oral premalignant lesions (OPLs) with genomic alterations have a heightened risk of evolving into oral squamous cell carcinoma (OSCC). Currently, genomic data are obtained through invasive tissue biopsy. Brush biopsy has been utilized for diagnosing dysplasia but its effectiveness in reflecting the complete genomic landscape of OPLs remains uncertain. This study investigates the potential of brush biopsy samples in accurately reconstructing the genomic profile of OPLs. The evolution and heterogeneity were assessed by assessing SNVs, copy number analysis, and subclonal architecture reconstruction of paired tissue-brush biopsy samples of oral epithelium, dysplastic lesion, and OSCC lesion. We found that brush biopsy accurately reflects the genomic landscape of oral lesions, mirroring about 90% of SNVs and comparable CNA profiles found in tissue biopsies. Genomic profiling with brush biopsy was tissue-specific, as SNVs identified in OPL or OSCC lesions were not found in adjacent normal mucosa. Shared SNVs and CNAs were observed between OPL and OSCC samples. This suggested a common ancestor giving rise to these lesions. Subclonal architecture reconstruction confirmed that both lesion types shared a common ancestor clone and then diverged evolutionarily. These findings underscore the potential of brush biopsies in accurately reconstructing the genomic profile of OPL and OSCC, highlighting their usefulness in understanding the biological processes involved in tumor evolution. Citation Format: Evit John, Tom Lesluyes, Toby Baker, Maxime Tarabichi, Peter Van Loo, Xiao Zhao. The genetic landscape of head and neck cancer using brush biopsy [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(6_Suppl):Abstract nr 1765.