Somatic mutation profiles in non-tobacco smoking and non-alcohol drinking South African female esophageal squamous cell carcinoma patients of African ancestry

Esophageal squamous cell carcinoma (ESCC) accounts for 85 % of the global esophageal cancer incidence, with a high disease burden in Eastern and Southern Africa. The etiology of ESCC is complex, with several factors such as tobacco smoking and alcohol consumption contributing to disease risk. Somatic mutations involved in the development of ESCC have been described but are under-studied in Africa. Our study reports the first whole-exome sequencing analysis of ESCC in a South African population who were not exposed to tobacco or alcohol. Fifteen female patients of African ancestry with ESCC who had never smoked or consumed alcohol were enrolled. Demographic and epidemiological data were obtained. DNA was extracted from matched blood and tumor tissue and subjected to whole exome sequencing. Bioinformatic analysis was used to identify somatic mutations, somatic copy number variations, and identify mutation signatures. The genes TP53 , MUC2 , KMT2D , and KMT2C were the most commonly mutated among genes previously reported to be mutated in ESCC tumors from other populations. The most common copy number variations detected were amplifications of chromosome 11q13, containing the CCND1 gene; 3q26, containing PIK3CA and SOX2 ; and 8q24, containing MYC . The most common mutation signature detected in the tumors was SBS5, associated with aging. Despite the lack of two major risk factors for ESCC in our patients, DNA sequencing detected somatic mutation profiles comparable to those found in patients from other populations, suggesting similar molecular pathways. This may stimulate their access to new therapeutic approaches developed in high-income countries. • We performed whole-exome sequencing on blood-tumour pairs of African, non-smoking, non-drinking female patients. • The most common type of somatic mutations identified were single nucleotide missense mutations. • The most commonly mutated genes among those previously described for ESCC were TP53, MUC2, KMT2D, and KMT2C. • The most common copy number variants detected were amplifications of chromosome 11q13, 3q26, and 8q24. • The most common mutation signature detected in the tumours was SBS5, associated with aging.