Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.

Journal Article (Journal Article)

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

Full Text

Duke Authors

Cited Authors

  • Liu, W; Snell, JM; Jeck, WR; Hoadley, KA; Wilkerson, MD; Parker, JS; Patel, N; Mlombe, YB; Mulima, G; Liomba, NG; Wolf, LL; Shores, CG; Gopal, S; Sharpless, NE

Published Date

  • October 6, 2016

Published In

Volume / Issue

  • 1 / 16

Start / End Page

  • e88755 -

PubMed ID

  • 27734031

Pubmed Central ID

  • PMC5053149

International Standard Serial Number (ISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.88755


  • eng

Conference Location

  • United States