1. A Genomic Analysis of Esophageal Squamous Cell Carcinoma in Eastern Africa.
- Author
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Van Loon, Katherine, Mmbaga, Elia J, Mushi, Beatrice P, Selekwa, Msiba, Mwanga, Ally, Akoko, Larry O, Mwaiselage, Julius, Mosha, Innocent, Ng, Dianna L, Wu, Wei, Silverstein, Jordyn, Mulima, Gift, Kaimila, Bongani, Gopal, Satish, Snell, Jeff M, Benz, Stephen Charles, Vaske, Charles, Sanborn, Zack, Sedgewick, Andrew J, Radenbaugh, Amie, Newton, Yulia, and Collisson, Eric A
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Human Genome ,Rare Diseases ,Digestive Diseases ,Genetics ,Good Health and Well Being ,Humans ,Esophageal Squamous Cell Carcinoma ,Esophageal Neoplasms ,Carcinoma ,Squamous Cell ,Genomics ,Tanzania ,Medical and Health Sciences ,Epidemiology ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundEsophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC.MethodsWe describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA).ResultsWe observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort.ConclusionsThis study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites.ImpactDespite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date.
- Published
- 2023