Abstract 2501: High mutation burden and ultraviolet light signature in conjunctival squamous cell carcinoma

Abstract Purpose: Conjunctival squamous cell carcinoma (conjSCC) is endemic in sub-Saharan Africa and is a major cause of ocular morbidity and mortality. This study aims to evaluate Tumor Mutation Burden (TMB), genomic signature, and histologic characteristics of conjunctival squamous cell carcinoma (conjSCC) in two cohorts of patients; one from the USA and one from Ethiopia. Methods: Whole exome sequencing data, PD-L1 expression, histologic features, and human papillomavirus (HPV) status were analyzed in conj SCC tumors of 25 patients treated at an Ethiopian (ETH) cancer center and 29 patients treated at a US cancer center. Genomic alterations in conjSCC were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas (TCGA). Results: TMB was found to be relatively high in conjunctival SCC (3.01/Mb, log10), was comparable to TMB values associated with cutaneous SCC, and was higher than most other SCC types available in the TCGA database. ETH samples had higher tumor mutational burden compared to the US cohort (3.34 vs 2.73). Solar elastosis was seen in a higher percentage of tumors from Ethiopia compared with the US cohort (78% vs. 10%). HPV status was similar between the cohorts (ETH: 21%, MDA: 28%). PD-L1 positivity defined as > 1% of tumor cells was seen in 33 of 53 tumors (62%). Mutations associated with ultraviolet light (UV) signature were the most frequently encountered signatures in both cohorts (SBS7b: 74% and SBS7a: 72%). UV signatures were more prevalent in the ETH cohort compared with the US cohort. Conclusions: Conjunctival SCC is associated with a high TMB providing the opportunity for immune checkpoint inhibitor therapy for patients with locally advanced and/or metastatic conjunctival SCC. Clinical trials are needed to assess the efficacy of immune checkpoint inhibitors in patients with conjunctival SCC, particularly in sub-Saharan Africa where this cancer is more frequently seen, and is associated with significant morbidity and mortality. Citation Format: Bita Esmaeli, Frederico O. Gleber-Netto, Oded Sagiv, Curtis R. Pickering, Neil Gross, Jing Ning, Melisachew M. Yeshi, Jonas Mitku, Michael T. Tetzlaff, Priyadharsini Nagarajan. High mutation burden and ultraviolet light signature in conjunctival 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(6_Suppl):Abstract nr 2501.