Esophageal Neoplasms study with RNA-Seq, WGS data on dbGaP (61 participants)

phs003217 — Molecular Determinants of Esophageal Cancer in Tanzania

<p>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 <a href="https://www.cancer.gov/ccg/research/genome-sequencing/tcga">The Cancer Genome Atlas Program (TCGA)</a>. 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. <a href="https://www.ncbi.nlm.nih.gov/gene/?term=7157">TP53</a> 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.</p>