Molecular Determinants of Esophageal Cancer in Tanzania

We describe the genomic profiles of 61 esophageal squamous cell carcinoma (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 Program (TCGA). Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis of ESCC from sub-Saharan Africa to date. We 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 and an absence of signature 29, which was previously reported in the Malawi cohort.]]>
This prospective study recruited sequential patients with suspected esophageal squamous cell carcinoma (ESCC) who sought care at Muhimbili National Hospital (MNH) in Tanzania. From May 2016 to February 2018, all patients ≥18 years old who presented to MNH with symptoms of dysphagia and were planned to undergo an endoscopy due to concern for a diagnosis of esophageal cancer were considered eligible for participation. Written informed consent was obtained from all participants prior to endoscopy. The final cohort included only those patients with pathologically confirmed ESCC.Non-permanent residents of Tanzania, and pregnant or lactating women were not eligible. ]]>